Pathogenic Microbiology Commons^™

Elucidating The Roles Of Septin Proteins In Thermotolerance And Cell Wall Integrity In Cryptococcus Neoformans, Stephani S. Martinez Barrera

All Dissertations

Cryptococcus neoformans is a globally distributed fungal pathogen responsible for causing cryptococcal meningitis in immunocompromised individuals. This pathogenic yeast must adapt to changes in temperature upon entering the human host. Septin proteins are conserved filament-forming GTPases that assemble as higher-order complexes at the cell cortex to support cytokinesis and morphogenesis in fungal and animal cells. In C. neoformans, four septin homologs (Cdc3, Cdc10, Cdc11, and Cdc12) assemble at the mother-bud neck, contributing to cytokinesis through poorly understood mechanisms. C. neoformans strains lacking the septins Cdc3 or Cdc12 are viable at 25°C, but fail to proliferate at 37°C, and are …

Characterizing The Role Of Pa5189 Of Pseudomonas Aeruginosa In Deletion And Overexpression Mutants, Seh Na Mellick

Theses/Capstones/Creative Projects

In the context of rising multidrug resistance in biofilm-forming pathogens like Pseudomonas aeruginosa, this study investigates the role of the understudied transcription factor PA5189 in antibiotic resistance and biofilm formation. PA5189 deletion and overexpression mutants were created in a parent P. aeruginosa strain using pEX18Tc-based recombinant suicide vectors, with genotypic verification of putative triparental conjugants achieved through restriction digestion and PCR. The study revealed that PA5189 overexpression significantly increases resistance to commonly used broad spectrum antibiotics such as ciprofloxacin and imipenem. Additionally, differential expression of PA5189 was found to notably affect biofilm formation, with variations contingent on the nutrient …

Characterization Of Ato Family Transporters In The Fungal Pathogen Cryptococcus Neoformans, Will Betsill

All Theses

Fungal pathogens are a significant threat to public health as they are becoming increasingly common and more resistant to treatment. Cryptococcus neoformans contributes greatly to this threat annually by causing an estimated 278,000 cases of cryptococcal meningitis resulting in approximately 181,000 deaths globally according to the CDC. C. neoformans is ubiquitous across most of the globe and can be found in such places as in trees or soil. Exposure to this fungus is especially dangerous to individuals who are immunocompromised or immunosuppressed. In these cases, inhalation of spores can lead to infection in the lungs. Once in the lungs, C. …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Managing Stress: A Study Of Stress Response Mechanisms In Mycobacteria, Augusto C. Hunt Serracin

Biology Dissertations

Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A …

Investigating Birds As Dispersal Vectors Of Litylenchus Crenatae Subsp. Mccannii (Anguinidae), The Nematode Associated With Beech Leaf Disease, Spencer Rock Parkinson

Graduate Theses, Dissertations, and Problem Reports

Beech leaf disease (BLD) is an emerging forest pathogen primarily affecting American beech (Fagus grandifolia, Ehrh.) in North America and has been attributed to tree mortality of sapling sized trees within five to seven years of infection. Symptoms typically occur in regenerating American beech thickets sprouting from roots of trees killed by beech bark disease. Scientists first observed BLD in Ohio in 2012 and currently has spread to 15 states in the USA and one Canadian province. The nematode Litylenchus crenatae subsp. mccannii (Lcm) is highly associated with BLD symptoms, interveinal chlorosis and defoliation of leaves, and is currently …

Overexpressing Two Helicobacter Pylori Small Rnas From A Bacterial Pathogenicity-Related Chromosomal Region To Investigate Their Regulation Of Virulence Genes, Roxanne N. Mcpeck, Olivia F. Morgan, Andrea R. Castillo Phd

2023 Symposium

The bacterial pathogen Helicobacter pylori infects the stomachs of approximately 50% of humanity, causing symptomatic disease (e.g., stomach ulcers, gastric cancer, and MALT lymphoma) in 10-15% of the infected. Colonizing the acidic, inhospitable stomach requires H. pylori to tightly regulate gene expression despite lacking many common bacterial genetic regulatory elements. The pathogen may compensate by using abundant non-protein-coding small RNAs (sRNAs) to regulate gene expression, including of infection-intensifying virulence genes. Additionally, severe disease and cancer correlate with infection by H. pylori strains that contain a nonessential chromosomal region, the cytotoxin-associated gene pathogenicity island (cagPAI). This encodes powerful virulence …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Diagnosis Of Urinary Tract Infections And Rapid Molecular Characterization Of Antibiotic Resistance, Mohammed Harris

All Dissertations

Urinary tract infections (UTIs) are one of the most common infectious clinical entities in both community and hospital settings. They have a broad range of clinical severity yet inflict large epidemiological burden of morbidity and mortality on patients and the healthcare system with billions of dollars in cost of treatment. Understanding what methods are optimal for diagnosing UTIs are critical to mitigate the marked impact and cost of these infections.

Chapter 1 and 2 in this work surveys the broad array of diagnostic modalities for UTIs and highlights their advantages and limitations in the context of the current standard of …

Crispr Technology As An Antiviral In Dsdna And Ssrna Viruses, Cathryn Mayes

Theses & Dissertations

The COVID-19 pandemic highlights the necessity of emergency response and pandemic preparedness, especially for emerging viral threats. Currently, virus-specific vaccines and antivirals are the primary tools to combat viral diseases; however, broad-spectrum antivirals that target more than one virus species could provide additional protection from emerging and re-emerging viral diseases (Andersen et al. 2020; Zhu et al. 2015; Hickman et al. 2022).

Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated endonucleases have become recently utilized as potential antiviral strategies due to their high specificity, efficacy, and versatility (Najafi et al. 2022). While CRISPR-based antivirals have previously been used to target specific …

Novel Signal Sequences And Fusion Partners For Paratransgenesis In Asaia, Christina Grogan

Electronic Theses and Dissertations

Mosquitoes transmit many pathogens that cause human disease. One such disease, malaria, is caused by parasites in the genus Plasmodium, infecting over 200 million people and killing over 600,000 per year. Current strategies to control vector-transmitted diseases are increasingly undermined by mosquito and pathogen resistance. Research has turned to additional and novel methods of control, such as altering the microbiota of the vectors. In this method, called paratransgenesis, symbiotic bacteria are genetically modified to affect the mosquito’s phenotype by engineering them to deliver antiplasmodial molecules into the midgut to kill parasites. These molecules must be released by the …

Identification And Characterization Of Genetic Elements That Regulate A C-Di-Gmp Mediated Multicellular Trait In Pseudomonas Fluorescens, Collin Kessler

Electronic Theses and Dissertations

Microbial communities contain densely packed cells where competition for space and resources are fierce. These communities are generally referred to as biofilms and provide advantages to individual cells against immunological and antimicrobial intervention, dehydration, and predation. High intracellular pools of cyclic diguanylate monophosphate (c-di-GMP) cause cells to aggregate during biofilm formation through the production of diverse extracellular polymers. Genes that encode c-di-GMP catalytic enzymes are commonly mutated during chronic infections where opportunists display enhanced resistance to phagocytosis and antibiotics. Our lab uses an emergent multicellular trait in the model organism Pseudomonas fluorescens Pf0-1 to study the emergence of c-di-GMP mutations …

Characterization Of Genetic Pathways Involved In Resistance To A Novel Antifungal Peptide, Kayla L. Haberman

Graduate Theses and Dissertations

Antibiotic resistance is increasing prevalence, particularly in Candida glabrata. This opportunistic pathogen is closely phylogenetically related to Saccharomyces cerevisiae; however, its characterization is limited. C. glabrata is only second to Candida albicans as a fungal pathogen in immunocompromised patients. Commonly resistant to azoles, the most common fungal therapy, it has become costly and challenging to treat. A histatin 5 derived antifungal peptide, KM29, has a high degree of efficacy in Candida species and S. cerevisiae. The objective of this work is to advance our understanding of the mechanism of action of KM29 against C. glabrata. Previous work in the lab …

Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn

Electronic Thesis and Dissertation Repository

To colonize human skin and survive within abscesses, Staphylococcus aureus has evolved mechanisms to evade host innate defenses. USA300 has become the predominate community-acquired methicillin-resistant S. aureus (CA-MRSA) clone, which can be in part attributed to detoxification of unsaturated free fatty acids (uFFA) found in sebum and the nares. Our lab has previously identified the TetR family regulator FarR responsible for induction of the resistance-nodulation-division (RND) superfamily efflux pump FarE to promote efflux of toxic uFFA. However, RND family efflux pumps remain poorly characterized in Gram-positive species and the mechanism by which FarR regulates FarE has yet to be determined. …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Identification Of Pneumococcal Membrane Proteins Involved In Colonization/Biofilm Formation And Cognate Host Cellular Receptors, Yoonsung Hu

Theses and Dissertations

Colonization is prerequisite for infection and transmission of Streptococcus pneumoniae, or pneumococcus. Currently available pneumococcal conjugate and pneumococcal polysaccharide vaccines can provide protection against a limited number of capsular serotypes. Implementation of vaccines has decreased the frequency of invasive pneumococcal disease and their colonization rates, but only in a serotype-dependent manner. This has led to serotype replacement in pneumococcal ecology and increased invasive disease caused by non-vaccine serotypes. Development of conserved protein-based vaccine that can provide protection against all pneumococcal serotypes is needed. Numerous surface proteins are conserved in all serotypes, and some are known to be involved in …

Telomeric And Sub-Telomeric Structure And Implications In Fungal Opportunistic Pathogens, Raffaella Diotti, Michelle Esposito, Chang Hui Shen

Publications and Research

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

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

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Optimization Of Rt-Qpcr Protocols To Quantify Chua Gene Expression In Campylobacter Jejuni Mutants Under Iron-Limited Conditions, Jacob D. Wilbert

Chancellor’s Honors Program Projects

No abstract provided.

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

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

Electronic Thesis and Dissertation Repository

Pathogenic streptococci have evolved specific systems to eliminate bacterial competitors within their biological niche. In microbial environments, niche competition is often driven by the production of short antimicrobial peptides called bacteriocins; this provides a mechanism by which Streptococcus pyogenes may compete for ecological stability and establish infection. Recent findings from our laboratory have identified two novel Class IIb bacteriocin systems – Streptococcus pyogenes bacteriocin (Spb) JK and MN in the M18 serotype S. pyogenes strain MGAS8232 – that may contribute to nasopharyngeal infection. Here, we show that galactose and CO₂ are distinct regulatory cues which induce antimicrobial activity. Under …

Phenotypic And Transcriptomic Characterization Of Colonial Phase Variation In The Cholera Pathogen Reveals A Novel Smooth Biofilm-Defective Form, Bliss Nicole Lambert

LSU Doctoral Dissertations

Biofilm formation, through the production of Vibrio polysaccharide (VPS), greatly enhances the environmental fitness and pathogenic success of Vibrio cholerae. As a result of phase variation, V. cholerae can switch from a smooth form to rugose, whose cells produce excess VPS, resulting in highly structured biofilms and greater resistance to stress. To further characterize the reversible process of phase variation, we isolated three colonial lineages. Each lineage began with a smooth parent, N16961, and contained a rugose variant derived from the parent, N16961R, as well as a smooth revertant of the rugose, N16961SD. We found clear phenotypic and transcriptomic …

Harnessing The Anopheles Microbiome To Conditionally Express Anti-Plasmodial Effectors During The Blood Meal, Jackie Shane

Electronic Theses and Dissertations

The control of vector-borne diseases such as malaria has been an extremely important research subject for hundreds of years. Because of the complex lifecycles of the pathogens that cause these diseases, finding a comprehensive treatment or preventative strategy has proven extremely difficult. Malaria alone is responsible for almost half a million deaths annually, most of them children under 5 years old. This disease is caused by parasitic protists in the genus Plasmodium that are transmitted to humans from Anopheles sp. mosquitoes. Most preventative strategies that are in use today revolve around controlling the vectors, including bed nets, insecticides, and larval …

The Characterization Of The Transcription Factor Msab And Its Role In Staphylococcal Virulence, Justin Batte

Dissertations

Staphylococcus aureus is a common human pathogen that is responsible for a wide range of infections, ranging from relative minor skin infections to life-threatening disease such as bacteremia, septicemia, and endocarditis. S. aureus possesses many different virulent factors that aid in its ability to cause this wide array of infections. One major virulence factor includes the production of capsular polysaccharide (CP). The production of CP plays a major role in the virulence response during infection specifically by providing S. aureus an antiphagocytic mechanism that allows the pathogen to evade phagocytosis during an infection. S. aureus has developed complex genetic regulatory …

Functional Similarity Of Prd-Containing Virulence Regulators In Bacillus Anthracis, Malik Raynor

Dissertations & Theses (Open Access)

Bacillus anthracis produces three regulators, AtxA, AcpA, and AcpB, that control virulence gene expression and are members of an emerging class of regulators termed “PCVRs” (Phosphoenolpyruvate-dependent phosphotransferase regulation Domain-Containing Virulence Regulators). AtxA controls expression of the toxin genes; lef, cya, and pag, and is the master virulence regulator and archetype PCVR. AcpA and AcpB are less well studied. AcpA and AcpB independently positively control transcription of the capsule biosynthetic operon capBCADE, and culture conditions that enhance AtxA activity result in capBCADE transcription in strains lacking acpA and acpB. RNA-Seq was used to assess the regulons of the …

A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well …

Comparison Between Listeria Sensu Stricto And Listeria Sensu Lato Strains Identifies Novel Determinants Involved In Infection, Jakob Schardt, Grant Jones, Stefanie Müller-Herbst, Kristina Schauer, Sarah E. F. D'Orazio, Thilo M. Fuchs

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The human pathogen L. monocytogenes and the animal pathogen L. ivanovii, together with four other species isolated from symptom-free animals, form the "Listeria sensu stricto" clade. The members of the second clade, "Listeria sensu lato", are believed to be solely environmental bacteria without the ability to colonize mammalian hosts. To identify novel determinants that contribute to infection by L. monocytogenes, the causative agent of the foodborne disease listeriosis, we performed a genome comparison of the two clades and found 151 candidate genes that are conserved in the Listeria sensu stricto species. Two factors were …

The Effect Of Diet On Midgut And Resulting Changes In Infectiousness Of Acmnpv Baculovirus In Trichoplusia Ni, Elizabeth Chen

Electronic Thesis and Dissertation Repository

The cabbage looper, Trichoplusia ni, a global generalist lepidopteran pest, has developed resistance to many synthetic and biological insecticides, requiring effective and environmentally acceptable alternatives. One possibility is the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). This baculovirus is highly infectious for T. ni, with potential as a biocontrol agent, however, its effectiveness is strongly influenced by dietary context. In this study, microscopy and transcriptomics were used to examine how the efficacy of this virus was affected when T. ni larvae were raised on different diets. Larvae raised on potato host plants had lower chitinase and chitin deacetylase transcript levels …

The Feoabc Locus Of Yersinia Pestis Likely Has Two Promoters Causing Unique Iron Regulation, Lauren O'Connor, Jacqueline D. Fetherston, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The FeoABC ferrous transporter is a wide-spread bacterial system. While the feoABC locus is regulated by a number of factors in the bacteria studied, we have previously found that regulation of feoABC in Yersinia pestis appears to be unique. None of the non-iron responsive transcriptional regulators that control expression of feoABC in other bacteria do so in Y. pestis. Another unique factor is the iron and Fur regulation of the Y. pestis feoABC locus occurs during microaerobic but not aerobic growth. Here we show that this unique iron-regulation is not due to a unique aspect of the Y. pestis …

Phenomenological And Molecular Basis Of The Cnidarian Immune System, Tanya Brown

FIU Electronic Theses and Dissertations

Coral reefs are one of the most diverse ecosystems on the planet due partially to the habitat structure provided by corals. Corals are long lived organisms that can live for hundreds of years and as a result growth of many species is very slow. As a result of this, recovery of corals from disease outbreaks is very slow and difficult and therefore the ecosystem is deteriorating rapidly. Due to this increase in disease and its detrimental effect on coral reefs, it has become imperative to study how corals respond to disease outbreaks. The response of the coral to pathogens is …