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Microbiology and Molecular Biology Theses and Dissertations

Theses/dissertations from 2024 2024.

Characterization of Cellular Metabolism Regulation by the Transcription Factor Centromere Binding Factor 1 (Cbf1) , Spencer Ellsworth

Connecting HIV-1 Viral Protein R Polymorphisms to Changes in Inflammatory Signals and Efficacy Testing of Essential Oils as Disinfectants Against SARS-CoV-2 , J. Brandon Lopez

The Effects of Combining β-lactam Antibiotics and Mefloquine in Multi-Drug ResistantPseudomonas aeruginosa , Kayla C. Maas

Laying Framework for a Novel In Vitro Eukaryotic System to Measure Rate of Transcription Elongation , John Lucas Ramirez

Theses/Dissertations from 2023 2023

Elucidating the Architecture of the TclIJN Complex that Converts Cysteine to Thiazoles in the Biosynthesis of Micrococcin , Diana G. Calvopina Chavez

Manipulating and Assaying Chromatin Architecture Around Enhancer Elements in vivo , John Lawrence Carter

Using de novo Transcriptomes to Decipher the Relationships in Cutthroat Trout Subspecies (Oncorhynchus clarkii) , Andrea Leena Kokkonen

Characterization of Phage-Host Interactions and its Impact on Tail Fiber Evolution , Jessica Marie Lewis

Halophilic Genes that Impact Plant Growth in Saline Soils , Mckay A. Meinzer

Characterizing Stress Granule Regulation by PAS Kinase, Ataxin-2 and Ptc6 and Investigating the Lifespan of Covid-19 Virus on Currency , Colleen R. Newey

Changes in RNA Expression of HuT78 Cells Resulting From the HIV-1 Viral Protein R R77Q Mutation , Joshua S. Ramsey

Theses/Dissertations from 2022 2022

Biofilm Characterization and the Potential Role of eDNA in Horizontal Gene Transfer in Hospital and Meat Isolates of Staphylococcus aureus and Their Biofilms , Ashley Lynne Ball

Novel Patterns for Nucleosome Positioning: From in vitro to in vivo , David Andrew Bates

The Effects of Polymorphisms of Viral Protein R of HIV-1 on the Induction of Apoptosis in Primary Cells and the Characterization of Twelve Novel Bacillus anthracis Bacteriophage , Jacob D. Fairholm

Analysis of the Cytopathogenic Effect of Different HIV-1 Vpr Isoforms on Primary Human CD4+ T Cells and a Model Cell Line , Jonatan Josue Fierro Nieves

The Role of Chitinase A in Mastitis-Associated Escherichia coli Pathogenesis , Weston D. Hutchison

Big Data Meta-Analyses of Transcriptional Responses of Human Samples to Orthohantavirus Infection and Shotgun Metagenomics From Crohn's Disease Patients. , John L. Krapohl

An Exploration of Factors that Impact Uptake of Human Papillomavirus Vaccines , David Samuel Redd

Genomic Analysis and Therapeutic Development of Bacteriophages to Treat Bacterial Infections and Parasitic Infestations , Daniel W. Thompson

The Use of Nucleotide Salvage Pathway Enzymes as Suitable Tumor Targets for Antibody-Based and Adoptive Cell Therapies , Edwin J. Velazquez

Comparative Sequence Analysis Elucidates the Evolutionary Patterns of Yersinia pestis in New Mexico over Thirty-Two Years , M. Elizabeth Warren

Regulation of T Cell Activation by the CD5 Co-Receptor and Altered Peptides, Characterization of Thymidine Kinase-Specific Antibodies, and Integrating Genomics Education in Society , Kiara Vaden Whitley

Theses/Dissertations from 2021 2021

Evolution and Selection: From Suppression of Metabolic Deficiencies to Bacteriophage Host Range and Resistance , Daniel Kurt Arens

Identifying Sinorhizobium meliloti Genes that Determine Fitness Outcomes , Alexander B. Benedict

Pushing the Limits of SARS-CoV-2 Survival: How SARS-CoV-2 Responds to Quaternary Ammonium Compounds and Wastewater , Benjamin Hawthorne Ogilvie

Mutations in HIV-1 Vpr Affect Pathogenesis in T-Lymphocytes and Novel Strategies to Contain the Current COVID-19 Pandemic , Antonio Solis Leal

Theses/Dissertations from 2020 2020

Staphylococcus aureus Metal Acquisition in Milk and Mammary Gland Tissue , Shalee Killpack Carlson

Antimicrobial Peptide Development: From Massively Parallel Peptide Sequencing to Bioinformatic Motif Identification , Alexander K. Erikson

A Comparison of Chikungunya Virus Infection, Dissemination, and Cytokine Induction in Human and Murine Macrophages and Characterization of RAG2-/-γc-/- Mice as an Animal Model to Study Neurotropic Chikungunya Disease , Israel Guerrero

The Effects of Immune Regulation and Dysregulation: Helper T Cell Receptor Affinity, Systemic Lupus Erythematosus and Cancer Risk, and Vaccine Hesitancy , Deborah K. Johnson

Identification of Genes that Determine Fitness, Virulence, and Disease Outcomes in Mastitis Associated Eschericia coli , Michael Andrew Olson

Theses/Dissertations from 2019 2019

Investigation of Thymidine Kinase 1 in Cancer Progression , Eliza Esther King Bitter

Ribosomally Synthesized and Post-Translationally Modified Peptides as Potential Scaffolds for Peptide Engineering , Devan Bursey

Bioaerosols Associated with Evaporative Cooler Use in Low-Income Homes in Semi-Arid Climates , Ashlin Elaine Cowger

PAS Kinase and TOR, Controllers of Cell Growth and Proliferation , Brooke Jasmyn Cozzens

Regulation of Immune Cell Activation and Functionby the nBMPp2 Protein andthe CD5 Co-Receptor , Claudia Mercedes Freitas

Characterizing Novel Pathways for Regulation and Function of Ataxin-2 , Elise Spencer Melhado

Interactions Between the Organellar Pol1A, Pol1B, and Twinkle DNA Replication Proteins and Their Role in Plant Organelle DNA Replication , Stewart Anthony Morley

SNFing Glucose to PASs Mitochondrial Dysfunction: The Role of Two Sensory Protein Kinases in Metabolic Diseases , Kai Li Ong

Characterizing the Function of PAS kinase in Cellular Metabolism and Neurodegenerative Disease , Jenny Adele Pape

Isolation, Characterization, and Genomic Comparison of Bacteriophages of Enterobacteriales Order , Ruchira Sharma

Isolation, Genetic Characterization and Clinical Application of Bacteriophages of Pathogenic Bacterial Species , Trever Leon Thurgood

Investigation of Therapeutic Immune Cell Metabolism , Josephine Anna Tueller

Theses/Dissertations from 2018 2018

Innate Immune Cell Phenotypes Are Dictated by Distinct Epigenetic Reprogramming , Kevin Douglas Adams

Bacteriophages for Treating American Foulbrood and the Neutralization of Paenibacillus larvae Spores , Thomas Scott Brady

Methods for Detection of and Therapy for Carbapenem-Resistant Enterobacteriaceae , Olivia Tateoka Brown

The Diversity Found Among Carbapenem-Resistant Bacteria , Galen Edward Card

Exploration of Antimicrobial Activity in Natural Peptides and High-Throughput Discovery of Synthetic Peptides , Emma Kay Dallon

Gut Microbiota Regulates the Interplay Between Diet and Genetics to Influence Insulin Resistance , Jeralyn Jones Franson

The Antimicrobial Properties of Honey and Their Effect on Pathogenic Bacteria , Shreena Himanshu Mody

The Ability of Novel Phage to Infect Virulent Bacillus anthracis Isolates , Hyrum Smith Shumway

Galleria Mellonella as an Alternate Infection Model for Burkholderia Species and a Comparison of Suspension and Surface Test Methods for Evaluating Sporicidal Efficacy , Joseph D. Thiriot

The Clinical Significance of HPRT as a Diagnostic and Therapeutic Biomarker for Hematological and Solid Malignancies , Michelle Hannah Townsend

Biomarker Analysis and Clinical Relevance of Thymidine Kinase 1 in Solid and Hematological Malignancies , Evita Giraldez Weagel

Hospital and meat associated Staphylococcus aureus and Their Biofilm Characteristics , Trevor Michael Wienclaw

Theses/Dissertations from 2017 2017

Comparison of Cytokine Expression and Bacterial Growth During Periparturient and Mid Lactation Mastitis in a Mouse Model , Rhonda Nicole Chronis

Influence of Epstein-Barr Virus on Systemic Lupus Erythematosus Disease Development and the Role of Depression on Disease Progression , Caleb Cornaby

The Effects of Nucleosome Positioning and Chromatin Architecture on Transgene Expression , Colton E. Kempton

Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter , Ramesh Krishna Vuppada

Acetobacter fabarum Genes Influencing Drosophila melanogaster Phenotypes , Kylie MaKay White

Theses/Dissertations from 2016 2016

The Path to Understanding Salt Tolerance: Global Profiling of Genes Using Transcriptomics of the Halophyte Suaeda fruticosa , Joann Diray Arce

Genetic and Biochemical Analysis of the Micrococcin Biosynthetic Pathway , Philip Ross Bennallack

Characterizing Interaction Between PASK and PBP1/ ATXN2 to Regulate Cell Growth and Proliferation , Nidhi Rajan Choksi

The Activity of Alkaline Glutaraldehyde Against Bacterial Endospores and Select Non-Enveloped Viruses , Justen Thalmus Despain

The Role of Viral Interleukin-6 in Tumor Development of Kaposi's Sarcoma-Associated Herpesvirus Lymphomas , Rebecca A. Fullwood

The Role of the Transcriptional Antiterminator RfaH in Lipopolysaccharide Synthesis, Resistance to Antimicrobial Peptides, and Virulence of Yersinia pseudotuberculosis and Yersinia pestis , Jared Michael Hoffman

A CryAB Interactome Reveals Clientele Specificity and Dysfunction of Mutants Associated with Human Disease , Whitney Katherine Hoopes

The pmrHFIJKLM Operon in Yersinia pseudotuberculosis Enhances Resistance to CCL28 and Promotes Phagocytic Engulfment by Neutrophils , Lauren Elizabeth Johnson

Characterization of Five Brevibacillus Bacteriophages and Their Genomes , Michael Allen Sheflo

Analysis of Nucleosome Isolation and Recovery: From In Silico Invitrosomes to In Vivo Nucleosomes , Collin Brendan Skousen

Human Herpesvirus 6A Infection and Immunopathogenesis in Humanized Rag2 -/-γc-/- Mice and Relevance to HIV/AIDS and Autoimmunity , Anne Tanner

Theses/Dissertations from 2015 2015

Identifying and Characterizing Yeast PAS Kinase 1 Substrates Reveals Regulation of Mitochondrial and Cell Growth Pathways , Desiree DeMille

The Detection and Molecular Evolution of Francisella tularensis Subspecies , Mark K. Gunnell

Isolation and Host Range of Staphylococcus aureus Bacteriophages and Use for Decontamination of Fomites , Kyle C. Jensen

The Antioxidant and DNA Repair Capacities of Resveratrol, Piceatannol, and Pterostilbene , Justin Ryan Livingston

High Salinity Stabilizes Bacterial Community Composition and Activity Through Time , Tylan Wayne Magnusson

Advancing Phage Genomics and Honeybee Health Through Discovery and Characterization of Paenibacillaceae Bacteriophages , Bryan Douglas Merrill

Specialized Replication Operons Control Rhizobial Plasmid Copy Number in Developing Symbiotic Cells , Clarice Lorraine Perry

Gene Networks Involved in Competitive Root Colonization and Nodulation in the Sinorhizobium meliloti-Medicago truncatula Symbiosis , Ryan D. VanYperen

Theses/Dissertations from 2014 2014

Snf1 Mediated Phosphorylation and Activation of PAS Kinase , Bryan D. Badal

Studies of PhoU in Escherichia coli: Metal Binding, Dimerization,Protein/Protein Interactions, and a Signaling Complex Model , Stewart G. Gardner

Pharmacologic Immunomodulation of Macrophage Activation by Caffeine , Ryan Perry Steck

Analysis of Nucleosome Mobility, Fragility, and Recovery: From Embryonic Stem Cells to Invitrosomes , Ashley Nicolle Wright

Enhancing Protein and Enzyme Stability Through Rationally Engineered Site-Specific Immobilization Utilizing Non-Canonical Amino Acids , Jeffrey Chun Wu

Theses/Dissertations from 2013 2013

Thymidine Kinase 1: Diagnostic and Prognostic Significance in Malignancy , Melissa Marie Alegre

Promoter Polymorphisms in Interferon Regulatory Factor 5 , Daniel N. Clark

Modulators of Symbiotic Outcome in Sinorhizobium meliloti , Matthew B. Crook

Evidences for Protein-Protein Interactions Between PstB and PhoU in the Phosphate Signaling Complex of Escherichia coli , Kristine Dawn Johns

Identification of the Binding Partners for HspB2 and CryAB Reveals Myofibril and Mitochondrial Protein Interactions and Non-Redundant Roles for Small Heat Shock Proteins , Kelsey Murphey Langston

A Quadruplex Real-Time PCR Assay for the Rapid Detection and Differentiation of the Burkholderia pseudomallei Complex: B. mallei , B. pseudomallei , and B. thailandensis , Chinn-woan Lowe

The Role of Nuclear BMP2 in the Cell Cycle and Tumorigenesis , Brandt Alan Nichols

Nuclear BMP2 and the Immune Response , Daniel S. Olsen

Hypersaline Lake Environments Exhibit Reduced Microbial Dormancy , Joshua Christopher Vert

Theses/Dissertations from 2012 2012

Characterization of the Cellular and Organellar Dynamics that Occur with a Partial Depletion of Mitochondrial DNA when Arabidopsis Organellar DNA Polymerase IB is Mutated , John D. Cupp

Effect of Antioxidants and Oxidative Stress on Different Cancer Cell Types , Gaytri Devi Gupta Elera

Effects of Chemical Stimulation and Tumor Co-Incubation on Macrophage Activation and Aggressiveness, Measured Through Phagocytosis and Respiratory Burst , Bo Marcus Gustafsson

Loss of the Lipopolysaccharide Core Biosynthesis rfaD Gene Increases Antimicrobial Chemokine Binding and Bacterial Susceptibility to CCL28 and Polymyxin: A Model for Understanding the Interface of Antimicrobial Chemokines and Bacterial Host Defense Avoidance Mechanisms , Cynthia S. Lew

Partial Characterization of the Antimicrobial Activity of CCL28 , Bin Liu

Characterizing the Role of HspB2 in Cardiac Metabolism and Muscle Structure Using Yeast and Mammalian Systems , Jonathan Paul Neubert

Humanized Mice as a Model to Study Human Viral Pathogenesis and Novel Antiviral Drugs , Freddy Mauricio Sanchez Tumbaco

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UKnowledge > College of Medicine > Microbiology, Immunology, and Molecular Genetics > Theses & Dissertations

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Theses/dissertations from 2024 2024.

AZITHROMYCIN ALCHEMY: A JOURNEY FROM PRECISION IMMUNOMODULATION TO TARGET EXPLORATION AND BEYOND , Hodaossadat Saghaeiannejad Esfahani

THE ROLE OF INTRACELLULAR GROWTH DURING THE SYSTEMIC SPREAD OF LISTERIA MONOCYTOGENES , Jamila S. Tucker

Theses/Dissertations from 2023 2023

Investigation of Key Mechanisms of Contact Dependent Growth Inhibition Systems in Burkholderia cepacia Complex Species , Zaria K. Elery

Investigating the relationship between metabolic reprogramming and peripheral CD4+ T-cell inflammation in human type 2 diabetes pathogenesis , Gabriella Kalantar

SUBSTRATE SELECTION AND EFFECTOR GATING IN THE HELICOBACTER PYLORI CAG TYPE IV SECRETION SYSTEM , Mackenzie E. Ryan

Theses/Dissertations from 2021 2021

APPLICATION OF GENETIC TECHNIQUES TO INVESTIGATE CHLAMYDIA TRACHOMATIS TYPE III SECRETION EFFECTOR BIOLOGY , Gabrielle Keb

CHARACTERIZING THE PHYSIOLOGY AND GENETICS OF CONTACT DEPENDENT GROWTH INHIBITON SYSTEMS IN BURKHOLDERIA SPECIES , Alice Elizabeth Oates

Theses/Dissertations from 2020 2020

Elucidating the Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury , Evan Lynch

MAST CELLS AS NOVEL EFFECTOR CELLS IN THE PATHOGENESIS OF CHRONIC GRAFT-VERSUS-HOST DISEASE , Ethan Strattan

Theses/Dissertations from 2019 2019

THE ROLE OF CD8 T CELL IMMUNODOMINANCE AND REGULATORY T CELLS IN NEONATAL IMMUNITY TO INFLUENZA VIRUS , Luke Heil

EVOLUTION OF THE ZHX TRANSCRIPTION FACTOR FAMILY AND ANALYSIS OF ZHX2 TARGET GENES CYP2A4 AND CYP2A5 IN MOUSE LIVER , Alexandra Nichole Nail

FUNCTIONAL ANALYSES OF THE DNA- AND RNA-BINDING PROTEIN SPOVG IN BORRELIA BURGDORFERI , Christina R. Savage

Theses/Dissertations from 2018 2018

INSIGHTS INTO KEY GENE REGULATORY NETWORKS IN BORRELIA BURGDORFERI , William Kenneth Arnold

THE ROLE OF PRO-INFLAMMATORY MEDIATORS IFNβ AND PROSTAGLANDIN E2 IN SUPPRESSION OF INNATE IMMUNITY TO LISTERIA MONOCYTOGENES , Michelle G. Pitts

Theses/Dissertations from 2017 2017

SUPPRESSION OF ANTI-TUMOR IMMUNITY IN CHRONIC LYMPHOCYTIC LEUKEMIA VIA INTERLEUKIN-10 PRODUCTION , Sara Alhakeem

ANTISENSE AFP TRANSCRIPTS IN MOUSE LIVER AND THEIR POTENTIAL ROLE IN AFP GENE REGULATION , Maria S. Dixon

IMMUNE EVASION BY DIVISION OF LABOR: THE TROPHIC LIFE CYCLE STAGE OF PNEUMOCYSTIS MURINA SUPPRESSES INNATE IMMUNITY TO THIS OPPORTUNISTIC, FUNGAL PATHOGEN , Heather M. Evans

ROLE OF INTRACELLULAR GROWTH DURING THE GASTROINTESTINAL STAGE OF LISTERIA MONOCYTOGENES INFECTION , Grant Steven Jones

NOVEL ROLE OF PROSTATE APOPTOSIS RESPONSE-4 TUMOR SUPPRESSOR IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA , Mary Kathryn McKenna

THERAPEUTIC POTENTIAL OF TARGETING REACTIVE OXYGEN SPECIES (ROS) STRESS IN MYELODYSPLASTIC SYNDROME (MDS) , Karine Z. Oben

Theses/Dissertations from 2016 2016

Expression of Zinc Fingers and Homeoboxes 2 (Zhx2) and Zhx2 Target Genes in Multiple Tissues of Wild-Type and Zhx2 Knockout Mice , Minen Al-Kafajy

Theses/Dissertations from 2015 2015

THE ROLE OF BATF2 IN LPS/IFNγ POLARIZED MACROPHAGES , Marie A. Gehman

Theses/Dissertations from 2013 2013

ON T CELL FATE DECISIONS: RETINOL, METABOLISM AND ITREG DIFFERENTIATION , Gavin I. Ellis

Theses/Dissertations from 2012 2012

Role of the Immune System and Bioactive Lipids in Trafficking Bone Marrow-Derived Stem Cells in Patients with Ischemic Heart Disease , Ahmed Abdel-Latif

INSIGHTS INTO HEPATIC ALPHA-FETOPROTEIN GENE REGULATION DURING LIVER DEVELOPMENT AND DISEASE , Erica Leigh Clinkenbeard

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Digital Commons @ USF > College of Arts and Sciences > Molecular Biosciences > Theses and Dissertations

Molecular Biosciences Theses and Dissertations

Theses/dissertations from 2024 2024.

Androgen Drives Melanoma Invasiveness and Metastatic Spread by Inducing Tumorigenic Fucosylation , Qian Liu

Theses/Dissertations from 2023 2023

Exploring strain variation and bacteriophage predation in the gut microbiome of Ciona robusta , Celine Grace F. Atkinson

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression , Janine M. DeBlasi

Thermodynamic frustration of TAD2 and PRR contribute to autoinhibition of p53 , Emily Gregory

Utilization of Detonation Nanodiamonds: Nanocarrier for Gene Therapy in Non-Small Cell Lung Cancer , Allan E. Gutierrez

Utilizing neoantigen-specific CD4* T cells and immune checkpoint modulation to advance adoptive cell therapy with tumor-infiltrating lymphocytes for metastatic melanoma patients , Maclean Scott Hall

Role of HLA-DRB1 Fucosylation in Anti-Melanoma Immunity , Daniel K. Lester

Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML , Christopher T. Letson

The Role of the DNA Helicase Rrm3 under Replication Stress , Julius Muellner

Regulated Intramembrane Proteolysis by M82 Peptidases: The Role of PrsS in the Staphylococcus aureus Stress Response , Baylie M. Schott

Histone Deacetylase 8 is a Novel Therapeutic Target for Mantle Cell Lymphoma and Preserves Natural Killer Cell Cytotoxic Function , January M. Watters

Theses/Dissertations from 2022 2022

Ceramide-1-Phosphate: A Novel Regulator of Golgi Fragmentation, Golgi-ER Vesicle Trafficking, and Anaplasma phagocytophilum Pathogenesis , Anika Nayar Ali

Regulation of the Heat Shock Response via Lysine Acetyltransferase CBP-1 and in Neurodegenerative Disease in Caenorhabditis elegans , Lindsey N. Barrett

Establishment of a Melanoma ESC-GEMM Platform and Its Use to Study PTEN Tumor Suppressor Functions , Ilah Bok

Adrenergic Modulation of Precursor Cells of Ovarian Cancer , Sweta Dash

Determining the Role of Dendritic Cells During Response to Treatment with Paclitaxel/Anti-TIM-3 , Alycia Gardner

To be or not to be: A Tale of Staphylococcal GpsB , Lauren R. Hammond

Origin and Epigenetic Regulation of Cutaneous T Cell Lymphoma , Carly M. Harro

Cell-free DNA Methylation Signatures in Cancer Detection and Classification , Jinyong Huang

The Role Of Eicosanoid Metabolism in Mammalian Wound Healing and Inflammation , Kenneth D. Maus

A Holistic Investigation of Acidosis in Breast Cancer , Bryce Ordway

Characterizing the Impact of Postharvest Temperature Stress on Polyphenol Profiles of Red and White-Fruited Strawberry Cultivars , Alyssa N. Smith

Identification of Secondary Structural Elements Contained Within the Intrinsically Disordered N-Terminal Tail of the Bloom’s Syndrome Helicase. , Vivek Somasundaram

Defining the role of Oxidized Mitochondrial DNA in Myelodysplastic Syndromes , Grace Anne Ward

Lord of the Z-rings: Uncovering the Role of MraZ and FtsL in Bacillus subtilis Cell Division , Maria Louise White

Theses/Dissertations from 2021 2021

Multifaceted Approach to Understanding Acinetobacter baumannii Biofilm Formation and Drug Resistance , Jessie L. Allen

Cellular And Molecular Alterations Associated with Ovarian and Renal Cancer Pathophysiology , Ravneet Kaur Chhabra

Ecology and diversity of boletes of the southeastern United States , Arian Farid

CircREV1 Expression in Triple-Negative Breast Cancer , Meagan P. Horton

Microbial Dark Matter: Culturing the Uncultured in Search of Novel Chemotaxonomy , Sarah J. Kennedy

The Multifaceted Role of CCAR-1 in the Alternative Splicing and Germline Regulation in Caenorhabditis elegans , Doreen Ikhuva Lugano

Unraveling the Role of Novel G5 Peptidase Family Proteins in Virulence and Cell Envelope Biogenesis of Staphylococcus aureus , Stephanie M. Marroquin

Cytoplasmic Polyadenylation Element Binding Protein 2 Alternative Splicing Regulates HIF1α During Chronic Hypoxia , Emily M. Mayo

Transcriptomic and Functional Investigation of Bacterial Biofilm Formation , Brooke R. Nemec

A Functional Characterization of the Omega (ω) subunit of RNA Polymerase in Staphylococcus aureus , Shrushti B. Patil

The Role Of Cpeb2 Alternative Splicing In TNBC Metastasis , Shaun C. Stevens

Screening Next-generation Fluorine-19 Probe and Preparation of Yeast-derived G Proteins for GPCR Conformation and Dynamics Study , Wenjie Zhao

Theses/Dissertations from 2020 2020

Understanding the Role of Cereblon in Hematopoiesis Through Structural and Functional Analyses , Afua Adutwumwa Akuffo

To Mid-cell and Beyond: Characterizing the Roles of GpsB and YpsA in Cell Division Regulation in Gram-positive Bacteria , Robert S. Brzozowski

Spatiotemporal Changes of Microbial Community Assemblages and Functions in the Subsurface , Madison C. Davis

New Mechanisms That Regulate DNA Double-Strand Break-Induced Gene Silencing and Genome Integrity , Dante Francis DeAscanis

Regulation of the Heat Shock Response and HSF-1 Nuclear Stress Bodies in C. elegans , Andrew Deonarine

New Mechanisms that Control FACT Histone Chaperone and Transcription-mediated Genome Stability , Angelo Vincenzo de Vivo Diaz

Targeting the ESKAPE Pathogens by Botanical and Microbial Approaches , Emily Dilandro

Succession in native groundwater microbial communities in response to effluent wastewater , Chelsea M. Dinon

Role of ceramide-1 phosphate in regulation of sphingolipid and eicosanoid metabolism in lung epithelial cells , Brittany A. Dudley

Allosteric Control of Proteins: New Methods and Mechanisms , Nalvi Duro

Microbial Community Structures in Three Bahamian Blue Holes , Meghan J. Gordon

A Novel Intramolecular Interaction in P53 , Fan He

The Impact of Myeloid-Mediated Co-Stimulation and Immunosuppression on the Anti-Tumor Efficacy of Adoptive T cell Therapy , Pasquale Patrick Innamarato

Investigating Mechanisms of Immune Suppression Secondary to an Inflammatory Microenvironment , Wendy Michelle Kandell

Posttranslational Modification and Protein Disorder Regulate Protein-Protein Interactions and DNA Binding Specificity of p53 , Robin Levy

Mechanistic and Translational Studies on Skeletal Malignancies , Jeremy McGuire

Novel Long Non-Coding RNA CDLINC Promotes NSCLC Progression , Christina J. Moss

Genome Maintenance Roles of Polycomb Transcriptional Repressors BMI1 and RNF2 , Anthony Richard Sanchez IV

The Ecology and Conservation of an Urban Karst Subterranean Estuary , Robert J. Scharping

Biological and Proteomic Characterization of Cornus officinalis on Human 1.1B4 Pancreatic β Cells: Exploring Use for T1D Interventional Application , Arielle E. Tawfik

Evaluation of Aging and Genetic Mutation Variants on Tauopathy , Amber M. Tetlow

Theses/Dissertations from 2019 2019

Investigating the Proteinaceous Regulome of the Acinetobacter baumannii , Leila G. Casella

Functional Characterization of the Ovarian Tumor Domain Deubiquitinating Enzyme 6B , Jasmin M. D'Andrea

Integrated Molecular Characterization of Lung Adenocarcinoma with Implications for Immunotherapy , Nicholas T. Gimbrone

The Role of Secreted Proteases in Regulating Disease Progression in Staphylococcus aureus , Brittney D. Gimza

Advanced Proteomic and Epigenetic Characterization of Ethanol-Induced Microglial Activation , Jennifer Guergues Guergues

Understanding immunometabolic and suppressive factors that impact cancer development , Rebecca Swearingen Hesterberg

Biochemical and Proteomic Approaches to Determine the Impact Level of Each Step of the Supply Chain on Tomato Fruit Quality , Robert T. Madden

Enhancing Immunotherapeutic Interventions for Treatment of Chronic Lymphocytic Leukemia , Kamira K. Maharaj

Characterization of the Autophagic-Iron Axis in the Pathophysiology of Endometriosis and Epithelial Ovarian Cancers , Stephanie Rockfield

Understanding the Influence of the Cancer Microenvironment on Metabolism and Metastasis , Shonagh Russell

Modeling of Interaction of Ions with Ether- and Ester-linked Phospholipids , Matthew W. Saunders

Novel Insights into the Multifaceted Roles of BLM in the Maintenance of Genome Stability , Vivek M. Shastri

Conserved glycine residues control transient helicity and disorder in the cold regulated protein, Cor15a , Oluwakemi Sowemimo

A Novel Cytokine Response Modulatory Function of MEK Inhibitors Mediates Therapeutic Efficacy , Mengyu Xie

Novel Strategies on Characterizing Biologically Specific Protein-protein Interaction Networks , Bi Zhao

Theses/Dissertations from 2018 2018

Characterization of the Transcriptional Elongation Factor ELL3 in B cells and Its Role in B-cell Lymphoma Proliferation and Survival , Lou-Ella M.m. Alexander

Identification of Regulatory miRNAs Associated with Ethanol-Induced Microglial Activation Using Integrated Proteomic and Transcriptomic Approaches , Brandi Jo Cook

Molecular Phylogenetics of Floridian Boletes , Arian Farid

MYC Distant Enhancers Underlie Ovarian Cancer Susceptibility at the 8q24.21 Locus , Anxhela Gjyshi Gustafson

Quantitative Proteomics to Support Translational Cancer Research , Melissa Hoffman

A Systems Chemical Biology Approach for Dissecting Differential Molecular Mechanisms of Action of Clinical Kinase Inhibitors in Lung Cancer , Natalia Junqueira Sumi

Investigating the Roles of Fucosylation and Calcium Signaling in Melanoma Invasion , Tyler S. Keeley

Synthesis, Oxidation, and Distribution of Polyphenols in Strawberry Fruit During Cold Storage , Katrina E. Kelly

Investigation of Alcohol-Induced Changes in Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics , Crystina Leah Kriss

Off-Target Based Drug Repurposing Using Systems Pharmacology , Brent M. Kuenzi

Investigation of Anemarrhena asphodeloides and its Constituent Timosaponin-AIII as Novel, Naturally Derived Adjunctive Therapeutics for the Treatment of Advanced Pancreatic Cancer , Catherine B. MarElia

The Role of Phosphohistidine Phosphatase 1 in Ethanol-induced Liver Injury , Daniel Richard Martin

Theses/Dissertations from 2017 2017

Changing the Pathobiological Paradigm in Myelodysplastic Syndromes: The NLRP3 Inflammasome Drives the MDS Phenotype , Ashley Basiorka

Modeling of Dynamic Allostery in Proteins Enabled by Machine Learning , Mohsen Botlani-Esfahani

Uncovering Transcriptional Activators and Targets of HSF-1 in Caenorhabditis elegans , Jessica Brunquell

The Role of Sgs1 and Exo1 in the Maintenance of Genome Stability. , Lillian Campos-Doerfler

Mechanisms of IKBKE Activation in Cancer , Sridevi Challa

Discovering Antibacterial and Anti-Resistance Agents Targeting Multi-Drug Resistant ESKAPE Pathogens , Renee Fleeman

Functional Roles of Matrix Metalloproteinases in Bone Metastatic Prostate Cancer , Jeremy S. Frieling

Disorder Levels of c-Myb Transactivation Domain Regulate its Binding Affinity to the KIX Domain of CREB Binding Protein , Anusha Poosapati

Role of Heat Shock Transcription Factor 1 in Ovarian Cancer Epithelial-Mesenchymal Transition and Drug Sensitivity , Chase David Powell

Cell Division Regulation in Staphylococcus aureus , Catherine M. Spanoudis

A Novel Approach to the Discovery of Natural Products From Actinobacteria , Rahmy Tawfik

Non-classical regulators in Staphylococcus aureus , Andy Weiss

Theses/Dissertations from 2016 2016

In Vitro and In Vivo Antioxidant Capacity of Synthetic and Natural Polyphenolic Compounds Identified from Strawberry and Fruit Juices , Marvin Abountiolas

Quantitative Proteomic Investigation of Disease Models of Type 2 Diabetes , Mark Gabriel Athanason

CMG Helicase Assembly and Activation: Regulation by c-Myc through Chromatin Decondensation and Novel Therapeutic Avenues for Cancer Treatment , Victoria Bryant

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Home > FACULTIES > Microbiology & Immunology > MNI-ETD

Microbiology & Immunology Theses and Dissertations

This collection contains theses and dissertations from the Department of Microbiology & Immunology, collected from the Scholarship@Western Electronic Thesis and Dissertation Repository

Theses/Dissertations from 2024 2024

Investigating the effects of physical maturation and sexual debut on HIV-1 susceptibility in adolescent males in Rakai, Uganda , Omar Almomani

Characterizing and Applying a Nasal Organotypic Model to Investigate the Effects of Immune Profile Types on SARS-CoV-2 Susceptibility , Victor H.K. Lam

Effect of sodium thiosulfate pre-treatment on renal ischemia-reperfusion injury , Pierce BR Nelson

Role of Ikzf3 as a Driver Mutation in B Cell Acute Lymphoblastic Leukemia , Heidi Rysan

Assessing Helicobacter pylori's HcpE and DsbK's Effects on Immunostimulation in Host Gastric Cells , Noor Salloum

Contribution of Streptolysin O and Streptolysin S to Streptococcus pyogenes Infections in HLA-Transgenic Mice , Blake A. Shannon

Regulation of ZAP-70 post-translational modifications by HIV-1 accessory proteins Nef and Vpu , Jack E. Teplitsky

Role of ETV5 Mutations in B Cell Acute Lymphoblastic Leukemia , Joshua S. Yi

Comparative Analysis of HIV-1 and SARS-CoV-2 Transmission Dynamics: Investigating Viral Fitness, Environmental Factors, and Pathogen-Host Interactions , Yiying Zhang

Investigating the role of two-component regulatory systems in regulating FnBP-A of Staphylococcus aureus , Yunqi Zhang

Theses/Dissertations from 2023 2023

The Effect of Kidney Preservation at 10°C with Hemopure and Hydrogen Sulfide Donor, Sodium Thiosulfate, in a Syngeneic Model of Rat Renal Transplantation , Maria Abou Taka

Mechanisms of lactic acid bacteria secretions as anti-Helicobacter pylori agents , Daelyn Carroll

Investigating the clinical and microbial factors contributing to calcium-containing kidney stone disease , John A. Chmiel

Elucidating the Biomechanics of MERTK-Mediated Efferocytosis , Brandon Hayato Dickson

SARS-CoV-2 infectivity potential in municipal wastewater: Implications for public health & water treatment , Justin Donovan

Development of a high-throughput approach for testing optimal fecal microbiota transplant material , Shaeley Jae Gibbons

The Role of Mucosa-Associated Invariant T Cells in an Autochthonous Mouse Model of Bladder Cancer , Inbar A. Habaz

Evaluating the role of GraS and FadXDEBA in promoting Staphylococcus aureus adaptation to host-derived fatty acids encountered at sites of colonization and infection , Robert C. Kuiack

The Effects of Cell Envelope Localization of FnBP-A on Staphylococcus aureus FnBP-A Dependent Phenotypes , Camille LeBlanc

The Role of the MEK1/2-ERK-RSK Signalling Axis in Innate Immune Memory , Rachel Low

Identification of a PU.1-regulated repressive region in Aicda gene locus , Allanna MacKenzie

Evolution of overlapping reading frames in virus genomes , Laura Muñoz Baena

Molecular Characterization of the Antiviral Properties of the Small HERC Family of Proteins , Ermela Paparisto

Effect of pharmacological inhibition of endogenous hydrogen sulfide production on bladder cancer progression , Sydney Relouw

Exploration of the Immune Landscape of EBV-associated Gastric Cancers , Mikhail Salnikov

Novel Roles of PACS-1 Within the Nucleus and the Regulated Secretory Pathway , Steven Trothen

Characterization of T-Cell Responses to Homocitrulline in a Mouse Model of Rheumatoid Arthritis , Sofya Ulanova

Inflammation in the Neovaginal Microenvironment of Transfeminine Individuals , Hannah M.J. Wilcox

Theses/Dissertations from 2022 2022

Investigation of the Binding and Outside-In Signalling Mechanisms of Anti-CD11d Acute Neurotrauma Therapy , Eoin N. Blythe

TetR family regulator FarR variation controls antimicrobial fatty acid efflux in Staphylococcus aureus , Camryn M. Bonn

The Role of Coagulase-Negative Staphylococcal Secreted Products on Staphylococcus aureus and Staphylococcus lugdunensis Infections , Denny Chin

Characterizing the Function of B Cells that Accumulate in the Inflamed Central Nervous System in Anti-Myelin Autoimmunity , Lika Chowdhury

The Streptococcus pyogenes hyaluronic acid capsule prevents neutrophil clearance, and greater insights into the streptococcal M protein as a vaccine candidate and driver of heart dysfunction , Jacklyn Hurst

In Vitro and In Vivo Characterization of the Metallodrug BOLD-100 as an Inhibitor of SARS-CoV-2 Replication , Daniel S. Labach

Regulation of MHC II Trafficking and Expression by Host and Viral Factors , Alex Lac

Design and Synthesis of Nef:SFK Interaction Inhibitors for Application in an Immune-directed HIV-1 Cure , Antony Lurie

Immunophenotyping and Functional Assessment of Antiviral CD8+ T Cells in a CLP Mouse Model of Immunosuppression , Alex R. Michaud

Herbicide Mediated Selection of Sulfonamide Resistant E. coli , Laura P. Muntz

Campylobacter jejuni Capsular Heptose: Moderation of Host Macrophages and Substrate Channeling During Synthesis , Matthew Myles

The role of reactive oxygen species in the accumulation of driver mutations in B cell acute lymphoblastic leukemia , Mia P. Sams

The Effect of Oral and Topical Antibiotics on Foreskin Inflammation and HIV Target Cells in Ugandan Men. , Zhongtian (Eric) Shao

Screening for purine transporters in S. aureus , Tothong Sonpaveerawong

The Expanding Roles of PACS-1 and PACS-2 in Cellular Physiology: Beyond Vesicular Protein Trafficking , Rong Xuan Zang

Theses/Dissertations from 2021 2021

Mucosa-Associated Invariant T Cells Undergo Phenotypic Changes Following Fecal Microbiota Transplantation , Jenna M. Benoit

Microbial innovations for disease management in honey bees , Brendan A. Daisley

Investigating the in vivo mechanism behind fibronectin binding protein-mediated hypervirulence of Staphylococcus aureus , Jaclyn A. Diamond

21°C is the emerging ideal temperature for kidney preservation in the presence of hydrogen sulfide , Smriti Juriasingani

Fishing for the right probiotic: Investigating the mechanism of mucosal-bacterial interactions at the interface of health and productivity in salmonid aquaculture , Luana Langlois

Testing a Novel Peptide-Infused Cream for Treatment of Rheumatoid Arthritis in DR4tg Mice , Alisha J. Moynahan

HIV-1 Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 non-B Subtypes , Emmanuel Ndashimye

Metabolic Reprogramming By DNA Tumour Viruses , Martin Prusinkiewicz

Metabolic origins of urogenital malodour in women and their relationship with their microbiota: can probiotics help? , Scarlett Puebla Barragan

The E26 Transformation-Specific-Family Transcription Factor Spi-C is Dynamically Regulated by External Signals in B Cells , Hannah L. Raczkowski

Generation and Characterization of an In Vitro Organotypic Foreskin Model for Future Study of the Penile Microbiome , Geoffrey J. Rempel

The impacts of psychological stress on innate-like invariant T cell survival, phenotype, and function , Patrick Rudak

A Workflow to Analyze ETHcD Mass Spectrometry Data for Studying HIV gp120 Glycosylation , Yingxue Sun

Meningeal B cells in central nervous system autoimmunity: Their phenotype and susceptibility to therapeutic depletion , Yodit Tesfagiorgis

Characterization and Discovery of Short Linear Motifs Mediating Protein Nuclear Import , Tanner M. Tessier

The Ability of Lactobacillus spp. to Limit Extracellular ATP Release by Urogenital Bacteria , Hannah Wilcox

Differential Effects of KIM-1 in Subcutaneous and Orthotopic Renca Models of Kidney Cancer , Demitra M. Yotis DY

Protective benefits of sodium thiosulfate-supplemented UW solution against prolonged cold ischemia-reperfusion injury during renal transplantation. , Max Y. Zhang Mr.

Theses/Dissertations from 2020 2020

Characterizing the Role of the Microbiome in Kidney Stone Disease , Kaitlin F. Al

Targeting CD5 to enhance immune T cell activation and function in treatment of solid tumours , Faizah Alotaibi

HPV Mediated Antagonism of the IL-18 Proinflammatory Pathway in Head and Neck Cancer , Wyatt W. Anderson

Investigation of the growth and survival of Staphylococcus aureus in CFTR-deficient macrophages , Bita Azad

Staphylococcus aureus small colony variants use heme and staphyloferrin B for iron acquisition , Izabela Z. Batko

Understanding Neonicotinoid Related Immunosuppression: A Potential for Beneficial Bacterial Intervention , John A. Chmiel

Exploiting the immunomodulatory potentials of iNKT cells in sepsis and cancer. , Joshua Choi

Optimizing Fecal Microbiota Transplantations For Therapeutic Use Beyond Clostridioides difficile Infection , Laura J. Craven

Cell-free DNA Release During Programmed Cell Death in Kidney Ischemia Reperfusion Injury , Alexander Dionne

The development of bacterial magnetic resonance imaging for microbiota analyses , Sarah C. Donnelly

Inducing DNA-Mismatch Repair Deficiency In Tumours: A Strategy To Enhance Anti-Tumour Immunity , Mikal El-Hajjar

Investigating the Regulation of Fatty Acid Efflux Pump FarE by TetR Family Regulator FarR in Staphylococcus aureus , Katherine A. Ferguson

Elucidating the Role of Host Tim-1 in Anti-tumour Immunity , Ingrid Hon

Kidney Injury Molecule-1 Mediated Phagocytosis and Its Therapeutic Application in Ameliorating Renal Transplant Ischemia Reperfusion Injury , Ji Yun Lee

B Cell Acute Lymphoblastic Leukemia is Driven by Activating Janus Kinase Mutations Cooperating with Spi1 and Spib Deletions in a Murine Model , Michelle Lim

Development and evaluation of a heterogenous virus-like particle (VLP) formulation to achieve HIV-1 latency reversal and cure. , Joshua P. Pankrac

Designing a Novel HIV-1 Candidate Vaccine , Rahul Pawa

Identification of the Signalosome and Signaling Pathway of the Efferocytic Receptor MERTK , Tarannum Tasnim

Theses/Dissertations from 2019 2019

Potential role of extracellular ATP released by bacteria in bladder infection and contractility , Behnam Abbasian

Brain-specific and systemic inflammatory response following repetitive concussive impact in a mouse model , So Young Eo

The Group A Streptococci Bacteriocins Facilitate a Competitive Advantage During Nasopharyngeal Infection , Lana Estafanos

The Epigenetic And Immune Landscapes Of HPV+ Tumor Microenvironments , Steven F. Gameiro

Utilizing FIV (Feline Immunodeficiency Virus) to develop a novel animal model to study HIV (Human Immunodeficiency Virus) , Ankita Suryakant Kambli

Designing An Optimal HIV-1 Env Immunogen For The Vesicular Stomatitis Virus Vaccine Platform And Elucidating The Role Of HIV-1 Nef In Env Trafficking , Jason Knapp

Novel insights into the genomic integration site landscape of HIV-1 and other retrovirus genera , Hinissan P. Kohio

The role of kidney injury molecule-1 in the metastasis of renal cell carcinoma , Jasper Lee

Encountering Lectins In The Recipient Mucosa: Implications Of N-linked Glycosylation On HIV-1 Transmission , Adam Meadows

Endogenous, controlled expression of anti-HIV-1 broadly neutralizing antibody , Darshit Patel

Role of the fibronectin-binding, collagen-binding, T-antigen region during nasopharyngeal infection by Streptococcus pyogenes , Akshay Sule

HIV-1 Group M Subtype Fitness, Disease Progression, and Entry Efficiency , Colin M. Venner

Mucosa-Associated Invariant T Cell Roles And Local Responses In Cell-Mediated Immunity To Influenza A Virus , Christine Marie Wardell

Metabolomic and Genomic Analysis of Lactobacillus crispatus Vaginal Isolates , Emiley Watson

Virally Packaged RNA in Virus-Like Particle Vaccines Enhances Antigenicity and Augments Latency Reversal of HIV-1 , Chanuka Wijewardhana

Determining the Relative Transmission Fitness of HIV-1 Subtypes A, B, C, and D , Spencer Yeung

The Role of Defective Macrophage Efferocytosis During Early Atherosclerosis in Humans , Charles Yin

Theses/Dissertations from 2018 2018

Characterization of Urinary Microbiome and Their Association with Health and Disease , Yige Bao

Characterization of interleukin (IL)-1β regulatory elements and chromatin conformation in macrophage activation , Woohyun Cho

Determining the Molecular Mechanisms of PACS-1-mediated Protein Sorting , Brennan S. Dirk

19F-MRI to Monitor Therapeutic Cell Migration and Distribution , Corby Fink

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Home > College of Medicine > Pathology and Microbiology > Theses & Dissertations

Theses & Dissertations: Pathology & Microbiology

Theses/dissertations from 2024 2024.

Development of Long-Acting Antiviral and Antimicrobial Prodrug Nanoformulations , Srijanee Das

Understanding the Role of Malondialdehyde-Acetaldehyde Adducts (MAA) in Inflammatory Bowel Disease , Megan L. Otte

A Tale of Two Proteins: An Investigation of Recruitment of Eukaryotic Proteins FLI1 And LRRF1 to the Chlamydial Inclusion Membrane , Natalie Sturd

Theses/Dissertations from 2023 2023

The Interface between Host and Bacterial Metabolism during Staphylococcus aureus Prosthetic Joint Infection , Blake P. Bertrand

Investigating Transcriptional Anomalies During Persistence in Chlamydia trachomatis , Nathan D. Hatch

Mechanisms of Mutated Myosin Vb Mediated Cholestasis in Microvillus Inclusion Disease , Melissa S. Holzapfel

Investigating Host Cell Transcriptional Heterogeneity and Metabolism in Staphylococcus aureus Biofilm Infections , Christopher M. Horn

Targeting the CXCR1/2 Axis in Pancreatic Ductal Adenocarcinoma , Caitlin Molczyk

Synergetic Signaling Between the Chlamydia Secreted Effectors TarP and TmeA Regulates Actin Kinetics and Efficient Entry , Matthew Romero

Investigating Plasmodial Proteostasis Mechanisms to Counter Artemisinin Resistance , Melissa Rosenthal

Understanding the Effect of Chikungunya Virus Infection on Bone Homeostasis , Enakshi Roy

Towards a Mode of Action for the Anti-Schistosomal Aryl Hydantoins , Thomas Schulze

Investigating and Targeting Iron Metabolism in Pseudomonas Aeruginosa and Klebsiella Pneumoniae , Zachary Scott

A Critical Assessment Of The Role Of ClpXP-Mediated Proteolysis In The Development and Differentiation Of Chlamydia trachomatis , Nicholas A. Wood

Theses/Dissertations from 2022 2022

Leukocyte Subsets in the Peripheral Blood and Spleen of Gastrointestinal Cancer Patients , Kathryn E. Cole

Exploring Host-Pathogen Interactions of the Ebola Virus Ribonucleoprotein Complex , M. Jane Morwitzer

Investigating the Role of Sphingosine Kinases During Alphavirus Infection , Opeoluwa Oyewole

Theses/Dissertations from 2021 2021

Role and Regulation of Staphylococcal Cell Death , Abdulelah Ahmed Alqarzaee S

Metabolic heterogeneity and the roles of CodY and CcpA in central metabolism and S. aureus biofilm formation. , Logan L. Bulock

The Staphylococcus Aureus lrgAB Operon Encodes a Holin-Like Protein Involved in Pyruvate Transport , Jennifer L. Endres

Neutrophils in Pancreatic Cancer Progression , Paran Goel

Understanding the Impact of Chlamydia Trachomatis Infection on Host Vesicular Trafficking , Lisa M. Jorgenson

Gene Expression Profiling of MAPK Pathway Inhibitor Resistance in Cutaneous Melanoma: Can Bioinformatics Be Used to Select Better Melanoma Cell Lines? , Stephen Luebker

Humanized Mice for Brain Infection of Emerging Viruses , Edward Makarov

Marinopyrrole Derivatives as Putative Antiparasitic Molecules Promoting Initiation of Programmed Cell Death in Toxoplasma gondii , Matthew C. Martens

Role Of Endocytic Machinery Regulators in EGFR Traffic and Viral Entry , Insha Mushtaq

Immunological Factors Associated with SIV/ SHIV Persistence in Diverse Tissue Niches , Omalla A. Olwenyi

Characterization of Di-Aryl Urea Compounds Against Acute and Chronic Toxoplasma Gondii , Austin Sanford

Molecular Pathogenesis of a Novel Subgroup of Peripheral T-cell Lymphomas , Jiayu Yu

The Role of VGLL4 and MARK2-HDAC axis in Mitosis and Cancer , Yongji Zeng

Theses/Dissertations from 2020 2020

Fundamental differences in the B cell locus, V(D)J repertoire, and Marburg virus epitope recognition of the Egyptian rousette bat that may allow for asymptomatic presentation , Maggie Linn Bartlett

Flavonoid and Cannabidiol Neural Glyoxalase Pathway Enhancement Against Aging and Alzheimer’s Disease , Joel R. Frandsen

Multistrain HIV-1 Elimination: A CRISPR-Cas9 and Theranostics-based Approach , Jonathan Herskovitz

Arginine Biosynthesis in Staphylococcus aureus , Itidal Reslane

Glycan-dependent adherence and skin colonization of Staphylococcus epidermidis mediated by the surface protein Aap. , Paroma Roy

Identification of Clonal Evolution Pattern and Mutation Event Associated with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Using Next-Generation Sequencing , Cheng Wang

Insights into the Chlamydial Niche: The Dynamic Roles of Inclusion Membrane (Inc) Proteins in Chlamydia trachomatis Development , Macy G. Wood

Theses/Dissertations from 2019 2019

The CXCR2-dependent role of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma , Mohammad Awaji

Molecular Insights into Major Peripheral T-cell Lymphoma Entities with Advances in a Representative Model System , Tayla B. Heavican

Mechanism of Bax/Bak Activation in Apoptotic Signaling , Kai Huang

Role of Rac1-Pak pathway in aggressive b-cell lymphoma , Tian Tian

IL-17-CXCR2 Axis Promotes Breast Cancer Metastasis and Therapy Resistance , Lingyun Wu

Monocyte Anti-Inflammatory Activity Is Dictated by Metabolic Status during Staphylococcus Aureus Biofilm Infection , Kelsey J. Yamada

Targeting Oncogenic Protein Sythesis in MYC-driven B Cell Lymphoma , Xuan Zhang

Acid Resistance Mechanisms in Staphylococcus aureus , Chunyi Zhou

The Role of Zyxin and LIMD1 in Mitosis and Cancer , Jiuli Zhou

Theses/Dissertations from 2018 2018

Francisella tularensis Insertion Sequence Elements Contribute to Differential Gene Expression , Amanda M. Bartling

The Role of Hippo Pathway in Mitosis and Cancer , Xingcheng Chen

Transcriptional regulation of icaADBC by IcaR and TcaR in Staphylococcus epidermidis , Tramy Hoang

MicroRNA expression and disease correlation in a Hispanic Lupus cohort , Thandiwe Jere

Dietary Polyunsaturated Fatty Acids Regulate Mammary Tumor Growth and Metastasis by Modulating Tissue Microenvironments , Saraswoti Khadge

Elucidation of the functions of Neuropilin 2 in osteoclasts in promoting prostate cancer bone metastasis. , Navatha S. Polavaram

Regulation of Canonical and Non-Canonical Hippo Pathway Components in Mitosis and Cancer , Seth Stauffer

Theses/Dissertations from 2017 2017

Focus: A Graph Approach for Data-Mining and Domain-Specific Assembly of Next Generation Sequencing Data , Julia Sommer

Redirection of the immune response to Staphylococcus aureus biofilm infection , Anna G. Staudacher

Functional Importance of Proline Transporters in Staphylococcus aureus , Dianne L. Wellems

Theses/Dissertations from 2016 2016

Genetic Predisposition and M1 Macrophage Polarization Created by Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation , Matthew A. Dale

The Role of Inflammatory Monocytes in Post-Influenza Methicillin-Resistant Staphylococcus aureus Pneumonia , Karl J. Fischer

Amino Acid Catabolism in Staphylococcus aureus , Cortney Halsey

Role of Stemloop D in Terminally Deleted Coxsackievirus B3 Replication , Lee K. Jaramillo

The Pathogenesis of Natural Killer/T Cell Lymphoma , Bei Jiang

Spatiotemporal Control of Staphylococcus aureus Biofilm Development , Derek E. Moormeier

Recurrent Mutations of T-Cell Receptor and CO-Stimulatory Signaling Proteins in Peripheral T-Cell Lymphomas , Joseph Rohr

Staphylococcus Aureus Biofilms Interfere With Macrophage Antimicrobial Responses Through Differential Gene Regulation, Toxin Production, and Purine Metabolism , Tyler D. Scherr

Mutations Affecting Epigenetic Regulators and Their Role in Peripheral T-Cell Lymphomas , Chao Wang

Regulation of cid-mediated cell death in Staphylococcus aureus , Ian H. Windham

The Role of CBL Family of E3 Ubiquitin Ligases in Intestinal Epithelial Homeostasis , Neha Zutshi

Theses/Dissertations from 2015 2015

The cruicial role of the endocytic recyling regulator EHD1 in mammalian development , Sohinee Bhattacharyya

Myeloid-derived suppressor cells contribute to the subversion of innate immunity during Staphylococcus aureus biofilm infection , Cortney E. Heim

Pax5 negatively regulates B lineage cell proliferation through inhibition of D cyclin expression , Dallas Jones

Molecular mechanism of LytSR signal transduction during biofilm formation , McKenzie Kristine Lehman

Role of Macrophages in Muscle Transfection with pDNA/PLURONIC Formulation , Vivek Mahajan

The Role of CXCR2 in Pancreatic Cancer Development and Progression , Abhilasha Purohit

Characterization of the Replication of Coxsackievirus B3 with a Mutationally Disrupted CRE(2C) and the use of Creatinine-Hydrochloride as an Antibacterial Agent , Shane E. Smithee

Identification of novel autoantibodies for lupus nephritis , Yinshi Yue

Role of Hippo-YAP signaling in Mitosis and Prostate Cancer , Lin Zhang

The Role of Genetic Alterations in Tumor Initiation, Progression and Transformation , Weiwei Zhang

Theses/Dissertations from 2014 2014

Detection of enteroviruses persistence in pancreas, spleen and heart , Abdulaziz Alhazmi

Life or death: maintaining bacterial homeostatis , Casey Matthew Gries

Staphylococcus epidermidis biofilm infection induces an anti-inflammatory response , Yenis Gutierrez-Murgas

TP73 in non-hodgkin lymphoma pathogenesis and therapy , Hesham M. Hassan

Characterization of influenza hemagglutinin vaccine immunogenicity and identification of novel anti-influenza therapeutics , Tess Kuenstling

Analyses of the functional antibody repertoire in chronic HIV-infected individuals , Hongyan Liao

Study of plasma cell repertoire in systemic lupus erythematosus and rheumatoid arthritis , Song Li

Study of competence for DNA transformation in Staphylococcus aureus , Katherine Leanna Maliszewski

Arginine Biosynthesis of Staphylococcus aureus , Austin S. Nuxoll

Mechanistic insights into the metabolic basics of therapy resistance in pancreatic cancer , Vinee Purohit

Contribution of Aap to Staphylococcus epidermidis virulence , Carolyn R. Schaeffer

Aberrant microglia and inflammasome function in juvenile Batten Disease , Juan Xiong

Novel phosphorylation of hippo-yap signaling pathway controls its oncogenic activity , Shuping Yang

Theses/Dissertations from 2013 2013

Regulation of rag-mediated V(D)J recombination and aberrant BCL2 to IGH translocation , Jirong Bai

A conceptual framework for capture, retention and utilization of pathologist knowledge using whole slide imaging , Walter Scott Campbell

On the identification of biologically relevant structures in aging and disease using systems biology and advanced network analysis , Kathryn M. Dempsey

The ribonuclease RnpA is a novel target for antimicrobial development , Tess Marie Eidem

Development and application of novel proteomic approaches for studying protein s-nitrosylation , Miao Liu

Molecular regulation of bacterial genes by small RNA molecules during cellular growth phases , Eric W. Miller

CXCR2 in breast cancer metastasis and therapy resistance , Bhawna Sharma

CXC chemokines in melanoma resistance to chemotherapy , Sheng Wu

Theses/Dissertations from 2012 2012

Tissue-reactive autoantibodies in systemic lupus erythematosus , Charles Hay

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• 1 University of Texas Medical Branch at Galveston, Galveston, Texas
• PMID: 21413252
• Bookshelf ID: NBK7627

Medical Microbiology begins with a review of the immune system, focusing on the body's response to invading microorganisms. Bacteria are then covered, first with a series of chapters presenting the general concepts of bacterial microbiology and then with chapters detailing the major bacterial pathogenes of humans. Similar sections cover virology, mycology, and parasitology. In each section, the introductory chapters stress the mechanisms of infection characteristic of that type of microorganism, thus providing the reader with a framework for understanding rather than memorizing the clinical behavior of the pathogens. The final section of the book Introduction to Infectious Diseases, is arranged by organ system and provides transition for clinical considerations.

Copyright © 1996, The University of Texas Medical Branch at Galveston.

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• Chapter 1. Immunology Overview
• Introduction to Bacteriology
• Chapter 2. Structure
• Chapter 3. Classification
• Chapter 4. Bacterial Metabolism
• Chapter 5. Genetics
• Chapter 6. Normal Flora
• Chapter 7. Bacterial Pathogenesis
• Chapter 8. Specific Acquired Immunity
• Chapter 9. Epidemiology
• Chapter 10. Principles of Diagnosis
• Chapter 11. Antimicrobial Chemotherapy
• Chapter 12. Staphylococcus
• Chapter 13. Streptococcus
• Chapter 14. Neisseria, Moraxella, Kingella and Eikenella
• Chapter 15. Bacillus
• Chapter 16. Miscellaneous Pathogenic Bacteria
• Chapter 17. Anaerobes: General Characteristics
• Chapter 18. Clostridia: Sporeforming Anaerobic Bacilli
• Chapter 19. Anaerobic Cocci
• Chapter 20. Anaerobic Gram-Negative Bacilli
• Chapter 21. Salmonella
• Chapter 22. Shigella
• Chapter 23. Campylobacter and Helicobacter
• Chapter 24. Cholera, Vibrio cholerae O1 and O139, and Other Pathogenic Vibrios
• Chapter 25. Escherichia Coli in Diarrheal Disease
• Chapter 26. Escherichia, Klebsiella, Enterobacter, Serratia, Citrobacter, and Proteus
• Chapter 27. Pseudomonas
• Chapter 28. Brucella
• Chapter 29. Pasteurella, Yersinia, and Francisella
• Chapter 30. Haemophilus Species
• Chapter 31. Bordetella
• Chapter 32. Corynebacterium Diphtheriae
• Chapter 33. Mycobacteria and Nocardia
• Chapter 34. Actinomyces, Propionibacterium propionicus, and Streptomyces
• Chapter 35. Leptospira
• Chapter 36. Treponema
• Chapter 37. Mycoplasmas
• Chapter 38. Rickettsiae
• Chapter 39. Chlamydia
• Chapter 40. Legionella
• Introduction to Virology
• Chapter 41. Structure and Classification of Viruses
• Chapter 42. Multiplication
• Chapter 43. Viral Genetics
• Chapter 44. Effects on Cells
• Chapter 45. Viral Pathogenesis
• Chapter 46. Persistent Viral Infections
• Chapter 47. Tumor Viruses
• Chapter 48. Epidemiology and Evolution
• Chapter 49. Nonspecific Defenses
• Chapter 50. Immune Defenses
• Chapter 51. Control of Viral Infections and Diseases
• Chapter 52. Chemotherapy of Viral Infections
• Chapter 53. Picornaviruses
• Chapter 54. Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae)
• Chapter 55. Togaviruses: Rubella Virus
• Chapter 56. Bunyaviruses
• Chapter 57. Arenaviruses
• Chapter 58. Orthomyxoviruses
• Chapter 59. Paramyxoviruses
• Chapter 60. Coronaviruses
• Chapter 61. Rhabdoviruses: Rabies Virus
• Chapter 62. Human Retroviruses
• Chapter 63. Rotaviruses, Reoviruses, Coltiviruses, and Orbiviruses
• Chapter 64. Parvoviruses
• Chapter 65. Norwalk Virus and Other Caliciviruses
• Chapter 66. Papovaviruses
• Chapter 67. Adenoviruses
• Chapter 68. Herpesviruses
• Chapter 69. Poxviruses
• Chapter 70. Hepatitis Viruses
• Chapter 71. Subacute Spongiform Unconventional Virus Encephalopathies
• Chapter 72. Filoviruses
• Introduction to Mycology
• General Concepts of Mycology
• Chapter 73. Basic Biology of Fungi
• Chapter 74. Disease Mechanisms of Fungi
• Chapter 75. Spectrum of Mycoses
• Chapter 76. Antifungal Agents
• Introduction to Parasitology
• Chapter 77. Protozoa: Structure, Classification, Growth, and Development
• Chapter 78. Protozoa: Pathogenesis and Defenses
• Chapter 79. Intestinal Protozoa: Amebas
• Chapter 80. Other Intestinal Protozoa and Trichomonas Vaginalis
• Chapter 81. Free-Living Amebas: Naegleria, Acanthamoeba and Balamuthia
• Chapter 82. Hemoflagellates
• Chapter 83. Malaria
• Chapter 84. Toxoplasma Gondii
• Chapter 85. Pneumocystis Carinii
• Chapter 86. Helminths: Structure, Classification, Growth, and Development
• Chapter 87. Helminths: Pathogenesis and Defenses
• Chapter 88. Schistosomes and Other Trematodes
• Chapter 89. Cestodes
• Chapter 90. Enteric Nematodes of Humans
• Chapter 91. Enteric Nematodes of Lower Animals Transmitted to Humans: Zoonoses
• Chapter 92. Filarial Nematodes
• Introduction to Infectious Diseases
• Chapter 93. Infections of the Respiratory System
• Chapter 94. Microbiology of the Circulatory System
• Chapter 95. Microbiology of the Gastrointestinal Tract
• Chapter 96. Microbiology of the Nervous System
• Chapter 97. Microbiology of the Genitourinary System
• Chapter 98. Microbial Infections of Skin and Nails
• Chapter 99. Microbiology of Dental Decay and Periodontal Disease
• Chapter 100. Bone, Joint, and Necrotizing Soft Tissue Infections

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• [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology]. Ruiz de Gopegui Bordes E, Serrano Mdel R, Orta Mira N, Ovies MR, Poveda M, Cardona CG. Ruiz de Gopegui Bordes E, et al. Enferm Infecc Microbiol Clin. 2011 Dec;29 Suppl 5:1-7. doi: 10.1016/S0213-005X(11)70037-4. Enferm Infecc Microbiol Clin. 2011. PMID: 22305663 Spanish.
• Opiate abuse, innate immunity, and bacterial infectious diseases. Wang J, Barke RA, Ma J, Charboneau R, Roy S. Wang J, et al. Arch Immunol Ther Exp (Warsz). 2008 Sep-Oct;56(5):299-309. doi: 10.1007/s00005-008-0035-0. Arch Immunol Ther Exp (Warsz). 2008. PMID: 18836861 Review.
• [Bibliometric analysis of publications on infectious diseases in Colombia, 2000-2009]. Ríos R, Mattar S, González M. Ríos R, et al. Rev Salud Publica (Bogota). 2011 Apr;13(2):298-307. Rev Salud Publica (Bogota). 2011. PMID: 22030887 Spanish.
• The Swiss Society of Microbiology: Small Bugs, Big Questions and Cool Answers. Greub G, Holliger C, Sanglard D, Schrenzel J, Thiel V, Viollier P. Greub G, et al. Chimia (Aarau). 2016 Dec 21;70(12):874-877. doi: 10.2533/chimia.2016.874. Chimia (Aarau). 2016. PMID: 28661360

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New Microbiological Techniques for the Diagnosis of Bacterial Infections and Sepsis in ICU Including Point of Care

Anna maria peri.

1 University of Queensland Centre for Clinical Research, Herston, Queensland 4029 Australia

Adam Stewart

2 Royal Brisbane and Women’s Hospital, Queensland Health, Herston, Queensland Australia

3 Central Microbiology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Herston, Queensland 4029 Australia

4 Queensland Children’s Hospital, QLD, Brisbane, Australia

Patrick N A Harris

Associated data.

Not applicable

Purpose of Review

The aim of this article is to review current and emerging microbiological techniques that support the rapid diagnosis of bacterial infections in critically ill patients, including their performance, strengths and pitfalls, as well as available data evaluating their clinical impact.

Recent Findings

Bacterial infections and sepsis are responsible for significant morbidity and mortality in patients admitted to the intensive care unit and their management is further complicated by the increase in the global burden of antimicrobial resistance. In this setting, new diagnostic methods able to overcome the limits of traditional microbiology in terms of turn-around time and accuracy are highly warranted. We discuss the following broad themes: optimisation of existing culture-based methodologies, rapid antigen detection, nucleic acid detection (including multiplex PCR assays and microarrays), sepsis biomarkers, novel methods of pathogen detection (e.g. T2 magnetic resonance) and susceptibility testing (e.g. morphokinetic cellular analysis) and the application of direct metagenomics on clinical samples. The assessment of the host response through new “omics” technologies might also aid in early diagnosis of infections, as well as define non-infectious inflammatory states.

Despite being a promising field, there is still scarce evidence about the real-life impact of these assays on patient management. A common finding of available studies is that the performance of rapid diagnostic strategies highly depends on whether they are integrated within active antimicrobial stewardship programs. Assessing the impact of these emerging diagnostic methods through patient-centred clinical outcomes is a complex challenge for which large and well-designed studies are awaited.

Introduction

Bacterial infections are common in adults and children admitted to the intensive care unit (ICU). In a cohort of 198 ICUs in 24 European countries, including 3147 patients, 37.4% had sepsis, with 24.7% presenting with sepsis on admission [ 1 ]. Infections in these patients are associated with significant morbidity, mortality and cost [ 2 ]. The risks associated with infection also result in high usage of antibiotics; in a global point-prevalence study, 70% of all ICU patients were receiving at least one antibiotic on any given day [ 3 ]. Being able to rapidly, and accurately, determine the causative pathogen in bacterial infections is a critical step in clinical management. Furthermore, with the growing global burden of antimicrobial resistance, rapid antimicrobial susceptibility testing (AST) is increasingly important to guide therapy. Given the necessity of reducing excessive antibiotic use, we also urgently need diagnostic strategies that can help exclude the presence of infection and define non-infectious inflammatory states for which antibiotics are not required [ 4 ].

Current diagnostic methods in patients presenting with sepsis largely rely on the culture of micro-organisms from blood to detect bacteraemia. However, not only is this approach relatively slow and laborious, culture-based systems suffer from a number of pre-analytical limitations that may affect performance, such as inadequate blood volume collection, prior antibiotic exposure and delays in laboratory processing or transportation, especially if laboratory facilities are off-site. Furthermore, even when an organism is cultured, definitive identification and susceptibility testing may be delayed for few days. Contamination is a frequent problem that may occur at blood culture (BC) collection and may drive inappropriate antibiotic use, misdirect clinical diagnosis and expose patients to unnecessary toxicities [ 5 ]. There are also many fastidious pathogens, which can be challenging to culture in standard automated systems [ 6 ].

While, in some respects, clinical microbiology laboratories have relied upon techniques that have evolved little for many decades, there are a number of emerging or newly established technologies that are set to revolutionise how microbial diagnostics may be performed in the near future. Mass-spectrometry methods were not part of routine laboratory practice a decade ago, yet matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF) has now rapidly replaced conventional bacterial identification methods in many laboratories, with step-wise improvements in turn-around times (TATs), accuracy and reduced costs [ 7 ]. This article aims to review the current state of the art, as well as new and emerging technologies, that may improve our capacity for rapid and accurate microbiological diagnosis in patients with significant bacterial infections and sepsis.

Established Rapid Diagnostic Methods

In recent years, implementation of existing rapid diagnostic technologies and improved automated workflow systems into clinical laboratories has enabled better delivery of healthcare [ 8 , 9 ]. Currently, automated BC systems are the gold standard for bloodstream infection detection [ 10 ]. Many automated BC systems exist (e.g. BACTEC TM FX, BacT/ALERT®) which apply different methods to detect organism growth (i.e. different nutrients and antimicrobial binding agents) and their performance has been compared [ 11 – 15 ]. In one study, a shorter time to detection and bacterial recovery rate was observed in the BacT/ALERT® VIRTUO system when compared to others [ 11 ]. Bottles containing antibiotic binding agents typically have better bacterial recovery rates [ 16 , 17 ]. Most automated BC systems have an internal sensor that detects carbon dioxide or pH as an indicator of microbial growth [ 18 ]. Microscopy and Gram stain on sterile fluids such as blood is a crucial step in providing critical information to inform diagnosis and management of severe infection. Despite automated Gram staining systems, interpretation remains laborious and time intensive, and is still operator dependent [ 19 ]. Automated image acquisition and machine learning–based approaches for automated Gram stain classifications have been explored, showing promising accuracy although still far from being able to perform as fully automated systems [ 20 ]. Early identification of important organisms such as Staphylococcus aureus directly from BC by coagulase testing has improved TAT and is inexpensive and easily incorporated into standard workflows [ 21 , 22 ]. Rapid antimicrobial susceptibility methods have been developed to reduce the time to results. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) has developed a standardised rapid method based on disc diffusion that offers antimicrobial susceptibility results within 4–8 h from BC positivity [ 23 – 25 ]. Detection of common mediators of resistance, such as β-lactamases, direct from clinical samples, is also possible. Rapid detection of clinically relevant carbapenemase- and extended-spectrum β-lactamase (ESBL)–producing organisms can be achieved through a variety of commercial assays (e.g. RAPIDEC® CARBA NP, ESBL-NP) [ 26 , 27 ]. Using a pH indicator to detect carbapenem hydrolysis, accurate and rapid (under 2 h) detection of carbapenemases from clinical isolates using a short incubation culture time can be demonstrated [ 28 ]. Similar reductions in TAT have been seen with rapid ESBL detection assays when compared with conventional susceptibility testing [ 29 ].

Direct antigen testing of clinical samples has aided in the rapid species identification. Urine antigen testing has been widely used for pathogen detection in respiratory infections caused by Legionella pneumophila and Streptococcus pneumoniae [ 30 ]. Antigens shed from these organisms and excreted in the urinary tract are usually detected by enzyme immunoassay (EIA) or lateral flow assay (LFA) [ 31 ]. Despite a shortened TAT, antigen testing suffers from poor sensitivity and specificity (for example, in children colonised with S. pneumoniae ) and is unable to provide antibiotic susceptibility profiles or other epidemiological data [ 32 ]. Rapid antigen detection from other clinical samples such as blood, throat swab, synovial fluid, pleural fluid and cerebrospinal fluid (CSF) has been examined previously but is not as commonly used in practice [ 33 – 35 ]. A large retrospective multicentre study assessed the clinical utility of rapid bacterial antigen detection using latex agglutination and concluded that they were costly and of no detectable clinical benefit [ 36 ]. Nucleic acid amplification testing (NAAT) or polymerase chain reaction (PCR) tests are a reliable non-culture microbial detection method, frequently used in laboratories around the globe for the diagnosis of a wide array of microbial pathogens. In addition, multiplex PCR incorporates several primers and probes within one reaction tube to amplify gene targets from multiple pathogens [ 37 ]. This highly sensitive approach increases the diagnostic yield and can be used on many clinical specimens including respiratory secretions, CSF, sterile fluids and diarrhoeal faeces. Limitations of PCR testing include reporting of incidental results, a lack of distinction between colonisation versus infection, requirement for experienced operators and a dedicated laboratory environment, and the absence of antibiotic susceptibility data [ 38 ]. Furthermore, PCR will only detect pathogens specifically targeted by the assay design. Rare and unexpected organisms, or strains with variants in target sequences, may be missed. The accuracy and favourable positive predictive value rests upon the correct clinical setting, e.g. Clostridoides difficile PCR testing in diarrhoea and multiplex bacterial PCR testing on CSF with pleocytosis.

The immune response to severe infection and sepsis is complex with a wide variety of inflammatory and anti-inflammatory mediators released [ 39 ]. Numerous biomarkers have been explored to assist in the rapid diagnosis of serious infections in ICU. Along with the leucocyte count, the most established of these is C-reactive protein (CRP). CRP is an acute phase protein that increases following interleukin-6 secretion by macrophages and T-cells, and has been shown to be a sensitive but not specific marker of sepsis [ 40 ]. Procalcitonin is a peptide secreted by many cells in the body in response to a pro-inflammatory stimulus, and may be more specific as a marker of bacterial infection than CRP [ 41 ]. The complexity of the host response is reflected in the range of biomarkers under investigation as potential markers of serious infection, including acute phase reactants, cytokines (in particular interleukin-6 and interleukin-8), soluble receptors and cell surface and endothelial markers [ 42 ]. Used individually or in combination, the role of biomarkers is to stratify the risk of serious infection, or crudely predict the likely aetiology and guide decisions on initiating or stopping antibiotics. Despite the limited nature of their predictions, evidence from randomised trials appears to support a role in ICU. While of limited value in guiding treatment initiation, the use of procalcitonin supported decisions to stop antibiotics, and reduced the duration of antimicrobial therapy in both adult and neonatal ICU [ 43 , 44 ].

New and Emerging Methods

In recent years, new rapid diagnostic tests (RDTs) have emerged that are able to provide pathogen identification and resistance profile within a short TAT. Their potential in improving patient management is promising although studies on their clinical impact remain scarce [ 45 ].

Emerging Diagnostics for Meningitis and Severe Respiratory Infections

Multiplex PCR are increasingly used in clinical practice for the diagnosis of central nervous system infections and pneumonia in the ICU setting. The BioFire FilmArray Meningitis/Encephalitis panel (bioMerieux) is an FDA-cleared, multiplex PCR detecting 14 pathogens from CSF in 1 h. Estimated sensitivity and specificity are 90 and 97% respectively [ 46 ] although evidence is scarce about its impact on patients’ outcomes [ 47 , 48 ].

Similarly, the BioFire FilmArray Pneumonia plus Panel can detect 27 microorganisms and 7 resistance markers on respiratory specimens, including nosocomial pathogens associated to hospital-acquired or ventilator-acquired pneumonia, and its role in improving antimicrobial stewardship (AMS) in critically ill patients with coronavirus disease 2019 has been suggested [ 49 ]. Other multiplex PCR (e.g. Seegene Allplex Respiratory panel) have narrower panels, more useful for community-acquired respiratory infections [ 50 ].

Nucleic Acid Detection from Blood Cultures

Several techniques are emerging for pathogen identification from positive BCs. The BioFire FilmArray BC identification panel (BCID, bioMérieux) is a multiplex PCR which detects 24 pathogens and 3 resistance genes from positive cultures with good analytical performance [ 51 , 52 ]. In a study on ICU patients with culture-confirmed sepsis, this test reduced the time to optimal treatment compared to standard BC [ 53 ] and a role in diagnosing ventilator-associated pneumonia has also been suggested [ 54 ]. A new version of this test has been recently released (BioFire BCID2) with a broader panel including 43 targets, although clinical evaluation studies are awaited.

In the specific setting of S. aureus bacteraemia, the Xpert MRSA/SA BC Assay (Cepheid) can detect through a real-time PCR methicillin-susceptible and methicillin-resistant S. aureus (MRSA) from positive BC. This test is associated with high sensitivity and specificity [ 55 ] and its automation easily fits the laboratory routine. Similarly, the Cepheid Xpert Carba-R assay is designed for the detection of genes encoding for carbapenemases from cultured bacterial isolates; however, it has been assessed as a method of direct detection from BC in settings with high carbapenem resistance prevalence [ 56 ]. The Verigene system (Luminex) uses multiplex PCRs and subsequent microarray hybridisation for detection of 22 bacteria and their resistance determinants from positive BC [ 57 , 58 ], and comprises two different panels, for Gram positives and Gram negatives, whose choice can be driven by the Gram stain results. Verigene has proved able to identify susceptibility to new β-lactam/β-lactamase inhibitors [ 59 ], and when implemented within an AMS program, reduced the time to optimal therapy in bacteraemic patients [ 60 , 61 ].

Other technologies applied to positive BC include fluorescent in situ hybridisation (FISH) using peptide nucleic acid (PNA) probes targeting 16S or 18S rRNA of bacteria and fungi respectively. PNA-FISH (AdvanDx) comprises 4 different panels and improvement of early treatment appropriateness has been demonstrated when integrated with AMS [ 62 , 63 ].

Pathogen Detection Direct from Blood

To skip the time-consuming step of BC growth, new technologies are emerging that may be used directly on whole blood. Among NAAT-based methods, Lightcycler SeptiFast Test (Roche) and Magicplex Sepsis Real-Time test (Seegene) are real-time PCR assays detecting several microorganisms and some markers of resistance from whole blood. Despite having broad panels, their low sensitivity [ 64 – 68 ] makes recommendations about their clinical use difficult. Indeed, SeptiFast was recently discontinued.

The combination of pathogen-specific PCR with miniaturised magnetic resonance has been realised in the T2 magnetic resonance (T2MR), able to identify microorganisms from whole blood with a brand-new methodology; specifically, the DNA amplified by PCR binds by complimentary probes to paramagnetic nanoparticles, whose signal is identified by T2MR [ 69 ]. The T2Candida test (T2 Biosystems) is an automated system which identifies the most common Candida species with high negative predictive values across a wide range of pre-test probabilities [ 70 , 71 ]. T2Candida has shown to shorten the time to effective antifungal therapy and reduce inappropriate empirical treatments, as well as to predict poor clinical outcomes in suspected and proven candidemia [ 71 ]. Similarly, the T2Bacteria detects the ESKAPE bacteria ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , Escherichia coli ) [ 72 – 74 ]. However, due to the limited panel of pathogens and resistance genes detected, its clinical benefit remains uncertain [ 75 ]. MALDI-TOF has been used directly on clinical samples including blood, urine [ 76 ] and CSF [ 77 ]. PCR/ESI-MS combines pathogen-specific PCR with mass spectrometry based on electrospray ionisation (ESI-MS): the IRIDICA system (Abbott) could detect 780 microorganisms and 4 resistance genes from various samples. However, despite promising performances, this assay has been discontinued [ 78 ] illustrating that a clear benefit of implementing these expensive tests is not yet apparent.

Direct Metagenomics

Metagenomics-based assays are among the most promising emerging tools in clinical microbiology as they can potentially identify any microorganisms in a given sample.

16S metagenomics is based on amplification through universal primers of the bacterial 16S rRNA gene, followed by amplicon sequencing, which leads to bacterial identification and taxonomic profiling [ 79 ]. SepsiTest (Molzym) is a semiautomated assay based on such technology used for pathogen detection from blood: despite being able to detect polymicrobial infections and fastidious organisms, its role in informing clinical decisions is limited as it suffers of low sensitivity and does not provide AST [ 64 ]. Compared to 16S metagenomics, shotgun metagenomics is based on untargeted next-generation sequencing (NGS), which reads complete bacterial genomes by massive parallel sequencing, providing a precise taxonomic resolution of all pathogens in a sample and potentially detects markers of antimicrobial resistance [ 80 ]. iDTECT Dx Blood (PathoQuest) is based on untargeted NGS and has been demonstrated to detect more clinically relevant microorganisms than conventional microbiology in immunocompromised patients, with a high negative predictive value [ 81 ]. Similarly, Karius NGS Plasma Test (Karius), which can identify microbial cell-free DNA from over 1200 microorganisms, showed 93.7% sensitivity compared to BCs in patients with suspected sepsis [ 82 ] and may be able to identify clinically relevant pathogens in blood in the days before the onset of bloodstream infections [ 83 ].

The ability of shotgun-metagenomics to perform a comprehensive analysis of the microbial genetic material in a biological sample holds great promise. However, limitations exist that make the implementation of these assays complex and a limited real-life clinical impact for diagnosis of infection has been reported by some studies [ 84 , 85 ]. The frequent detection of contaminants and colonisers affects NGS specificity and complicates the interpretation of results in diagnosing bloodstream infections; to address this limitation, a recent study on patients with septic shock showed the utility of the sepsis indicating quantifier (SIQ) score as a means of discriminating clinically relevant pathogens from the others [ 86 ]. Moreover, NGS sensitivity is decreased in samples with high nucleic acid background such as blood, thus requiring human DNA depletion. Such techniques also lack standardisation of analysis methods. Frequently, bioinformatics skills needed to analyse NGS data are unavailable in a standard diagnostic laboratory and may require external expertise or data transfer to other facilities. This introduces delays, as well as additional costs, challenges in computational and data storage capacity, data privacy issues and complexities for accreditation with regulatory authorities.

New Rapid AST Methods

The detection of resistance genes is not always reliable to reflect the actual susceptibility pattern of the identified pathogen. The FDA-approved Accelerate Pheno system (Accelerate Diagnostics) can detect 16 microorganisms from positive BC based on FISH technology as well as perform phenotypic AST by morphokinetic cellular analysis [ 87 – 89 ], with over 96% categorical agreement in comparison to standard methods [ 89 , 90 ] (Table ​ (Table1). 1 ). Studies showed this test improves achievement of and time to optimal therapy in patients with bacteraemia [ 92 , 93 ].

Commercially available rapid diagnostic tests for the diagnosis of bloodstream infections

TAT , turn-around time; PCR , polymerase chain reaction; MRSA , methicillin-resistant S. aureus ; CoNS , coagulase-negative staphylococci; PNA , peptide nucleic acid; FISH , fluorescent in situ hybridisation; AST , antimicrobial susceptibility testing; MIC , minimum inhibitory concentration; ID , identification

a Including sample shipment

Advances in microfluidics, electronics, optic and biosensor techniques are promising approaches for next-generation rapid AST and at the early stages of translation into practice. Evidences on their role to address point of care testing (POCT) needs, however, are still scarce, and studies are still in progress to achieve FDA approval and CE mark [ 94 ].

Table ​ Table1 1 summarises performance of the main commercially available RDTs for bloodstream infections.

Host Response and Transcriptomics

Existing biomarkers provide a limited insight into the complex host response to infection, and consequently offer limited discrimination between infectious aetiologies. Indeed, commonly used infection biomarkers offer only a binary outcome of severity of infection, or probability of bacterial infection to guide antibacterial use. There is growing interest in the role of omics technologies to interrogate the proteome, metabolome, epigenome or transcriptome to more comprehensively characterise infection phenotypes. Such biological classifiers are established in the fields of oncology [ 95 ] and cardiovascular disease [ 96 ], though the time-critical nature of infections in ICU adds a further challenge. Diagnostics based on differential gene expression in acute infections are of substantial interest. Classifiers such as the ‘Integrated Antibiotics Decision Model’ [ 97 ] and a ‘Disease Risk Score’ in febrile children [ 98 ] have undergone external validation to suggest they have potential value in guiding treatment decisions. Septicyte was the first such transcript-based infectious disease diagnostic to receive FDA approval in 2017 and continues to undergo external validation to demonstrate its value in different clinical contexts [ 99 ]. Transcript-based classifiers have the potential to characterise patients not only by pathogen (bacterial, viral or fungal) but by inflammatory phenotype thereby offering the possibility of successful personalised immunomodulation in sepsis [ 100 ]. Establishing the role of transcript-based disease classifiers in infections on ICU will require an understanding of how such assays can be performed in a timely way, and a demonstration of their impact, including cost-effectiveness, in clinical trials.

How Should the Clinical Utility of Novel Rapid Diagnostics Be Evaluated?

Reduced turn-around time (TAT) in either identification or susceptibility information is not sufficient to indicate the improved utility of a test, though it is an important component [ 101 ]. Other parameters include the sensitivity, specificity, type of result yielded and the confidence of the relevant clinician acting upon the result [ 102 ]. Arguably, a full assessment of the impact and value of rapid diagnostic microbiology technologies evaluates more than TATs and AMS outcomes. We need controlled trials or interrupted time series analyses over extended periods, evaluating multiple key clinical and process outcomes such as mortality, acute kidney injury, length of stay and readmission. This would ideally be combined with a comprehensive cost-effectiveness analysis, assessing not only hospital admission costs, but value of quality-adjusted-life-year (QALY) saved, costs of laboratory implementation of RDT programs and adjunct AMS programs.

There is a paucity of high-quality evidence in this field, though there are numerous quasi-studies that have evaluated AMS outcomes with several incorporating a selection of clinical or process outcomes [ 45 , 103 , 104 ]. The most consistent, though not universal finding, has been that rapid technologies alone do no translate even to better AMS outcomes, let alone improved clinical outcomes, without also embedding customised AMS support strategies and this is reflected in the Infectious Diseases Society of America (IDSA) guidelines [ 45 , 52 , 101 , 105 , 106 ].

Targeted AMS strategies that have been evaluated to support implementation of RDT range from extended hours of the service, notification of critical results to a member of the AMS team who provides targeted direct advice and other activities that increase clinical interaction [ 105 , 107 ]. When these strategies are coupled with RDTs, improvements in optimal antimicrobial use and de-escalation are the most consistent findings, with cost saving the least represented [ 45 , 108 , 109 ]. Impact on clinical outcomes has been highly variable in studies assessing length of stay, mortality and re-admission [ 110 – 112 ]. The reasons for this have not been rigorously studied but based on other stewardship research likely pertain to prescribing behaviour, lack of familiarity, and experience or expert knowledge in the actionability of RDT results [ 113 , 114 ]. The likelihood of a clinical de-escalation of antimicrobials overnight is low, even if microbiology and AMS teams extend their hours of operation for a 24/7 model, reflecting most likely a combination of either junior clinical staff or caretaker culture overnight [ 105 ].

The most actionable results include (i) identification of likely contaminants and (ii) detection of a molecular target correlated with resistance not covered by the empiric regimen. One of the molecular RDTs most rigorously assessed for AMS and clinical impact has been the Verigene system. The results for Gram-positive BC organisms were demonstrably more actionable than for Gram negatives, reflecting both the complexity of genetic markers of resistance and the morbidity and mortality associated with early suboptimal treatment of Gram-negative sepsis [ 105 ]. Multiplexed PCR assays are limited in the number of target genes that can be identified and do not comprehensively cover all relevant resistance mechanisms. Despite this, Verigene has outperformed clinical risk tools for predicting third-generation cephalosporin resistance, though the applicability of this result will be variable depending on the community prevalence of ESBL, in particular [ 107 ]. Another significant limitation of most molecular RDT systems is the sub-optimal sensitivity in detecting polymicrobial infection limiting confidence in de-escalation [ 105 ].

Implementation of molecular RDTs is a relatively resource-intensive measure and current technologies are not stand-alone tests. Conventional phenotypic testing would still need to be performed, particularly for AST [ 115 ]. As discussed above, molecular RDT does have some significant limitations including decreased sensitivity in detecting polymicrobial bacteraemia, the potential for cross-contamination or genetic similarity (e.g. Shigella and E. coli ), the restricted range of resistance mechanisms and the lack of clinically validated correlation of genetic makers with minimum inhibitory concentrations (MICs). The latter can be critical to therapeutic drug monitoring and wild-type surveillance or to determine suitability of use of an agent such as meropenem even in the presence of a carbapenemase. Phenotypic RDTs and biomarkers are also usually utilised in conjunction with conventional testing. Improved cost-efficiencies can be associated with targeted use for critically unwell patients, specifically within intensive care, haematology and oncology [ 113 ].

Demonstrating benefits from introduction of such services will depend on the institution including local antibiograms, patient complexity and strength of current AMS, and interactions with microbiology and infectious disease teams [ 109 ]. Low- and middle-income nations with high rates of community multidrug-resistant organisms may find the costs of molecular methods prohibitive but rapid phenotypic tests or optical sensor portable low footprint techniques may have a significant role [ 116 ].

Point of Care Diagnostics

Most of the methods discussed thus far require a well-functioning laboratory, with at least a basic requirement for scientific skills and training. Only assays which are simple to use and have a low risk of incorrect results are generally approved for POCT, with higher complexity tests reserved for suitably equipped laboratories. However, using a laboratory-based test introduces some delay and a degree of distance from the patient and treating clinicians. In geographically dispersed countries with remote locations, this can result in major delays for critical tests such as BCs or molecular diagnostics. In Australia, as in most other jurisdictions, organisations offering POCT must adhere to certain standards that define appropriate governance, maintenance of test integrity, minimisation of pre-analytical, analytical and post-analytical errors, provision of suitable training and competency assessment, with all such processes embedded within a robust quality management system [ 117 ]. Such processes have evolved over time to ensure that clinicians have confidence in test results they receive. Currently, no POCT exists for the accurate diagnosis of bloodstream infections or most other critical infections. The future holds some hope for technological advances such as microfluidic devices that can integrate sampling handling and signal generation within a POCT setting, maybe using testing platforms such as “on-chip” immunoassays or nucleic acid analysis. Such technology can, in theory, incorporate all the key steps of molecular detection: cell lysis and extraction, nucleic acid purification, amplification and detection of reaction products. Such miniaturisation may also allow multiplexing to enable high-throughput testing within a single portable device [ 118 ]. There is substantial pre-clinical research into the design, construction materials and detection technologies for such devices, but as yet no commercial products are ready for clinical evaluation.

Conclusions

It is likely that a number of new microbiological methods will enhance our capacity to rapidly and accurately identify pathogens in critically unwell patients. However, well-designed studies assessing key clinical outcomes are needed to define their role in improving the management of severe infections.

Availability of Data and Material

Code availability, declarations.

PNAH reports grants from Shionogi, MSD and Sandoz, as well as personal fees from Sandoz and Pfizer, outside the submitted work. All the other authors declare no conflicts of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.

This article is part of the Topical Collection on Sepsis in the ICU

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