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Articles 1 - 21 of 21
Full-Text Articles in Pathogenic Microbiology
Conformational Rearrangements In The Sensory Rcsf/Omp Complex Mediate Signal Transduction Across The Bacterial Cell Envelope, Sarah Rosemarie Lach Phd
Conformational Rearrangements In The Sensory Rcsf/Omp Complex Mediate Signal Transduction Across The Bacterial Cell Envelope, Sarah Rosemarie Lach Phd
Dissertations & Theses (Open Access)
Timely detection and repair of envelope damage are paramount for bacterial survival. The Regulator of Capsule Synthesis (Rcs) stress response is a complex signaling cascade that monitors gram-negative cell envelope integrity and can transduce the stress signals across the multilayered envelope to regulate gene expression in the cytoplasm. The outer membrane (OM) lipoprotein RcsF is the sensory component, but how RcsF functions remains elusive. RcsF interacts with the β-barrel assembly machinery (Bam) complex, which assembles RcsF in complex with OM proteins (OMPs), resulting in RcsF’s partial cell surface exposure. RcsF can also interact with the periplasmic domain of the negative …
The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And Toxin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes
The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And Toxin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes
Dissertations & Theses (Open Access)
AtxA, the master virulence gene regulator in Bacillus anthracis, is a PRD-containing virulence regulator (PCVR) as indicated by the crystal structure, post-translational modifications, and activity of the protein. PCVRs are transcriptional regulators, named for the regulatory domains subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS), termed PTS Regulatory Domains (PRD), and for their impact on virulence gene expression. Generally, the phosphorylation of a PCVR regulates protein activity and multimerization. AtxA is phosphorylated at two histidine residues - one in each of its two PRDs. Phosphorylation at position 199 allows for AtxA to positively affect expression of virulence genes, whereas …
Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely
Investigation Of Novel Virulence Mechanisms In Candida Albicans, Elisa Marie Tafoya Vesely
Dissertations & Theses (Open Access)
Candida albicans is the most important fungal species associated with humans. Normally present in the human microbiome as a commensal colonizer, C. albicans is also the fourth most prevalent organism isolated from bloodstream infections in hospitals. Disseminated infections have an associated mortality rate of around 40%. The results of the work described in this dissertation cover the broad subject of C. albicans adaptation to the host and the mechanisms by which this organism is able to survive and cause infection through a variety of means. A key determinant in disease progression is interaction with innate immune cells, specifically macrophages and …
Functional Similarity Of Prd-Containing Virulence Regulators In Bacillus Anthracis, Malik Raynor
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 …
Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham
Mechanism Of Candida Albicans Biofilm And Virulence Inhibition By A Bacterial Secreted Factor, Carrie Graham
Dissertations & Theses (Open Access)
The human microbiome is a diverse polymicrobial population comprised of both fungi and bacteria. Perturbations of the normal microbiome can have a profound impact on health, including the development of infections. Exploitation of these polymicrobial interactions has the potential to provide novel treatment and prevention strategies for infectious diseases. Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species are also amongst the most important and problematic, opportunistic nosocomial pathogens and are often co-isolated during infection. Surprisingly, these two species antagonize each other’s …
Evaluating The Impact Of Post-Translational Modifications By The Secreted Zinc Metalloprotease, Gele, On The Major Autolysin Of E. Faecalis, Atla, And A Stress-Induced Protein, Salb, Emily K. Stinemetz
Dissertations & Theses (Open Access)
AtlA is the major peptidoglycan hydrolase of E. faecalis involved in cell separation of dividing cells. SalB is a secreted stress-induced protein regulated by the CroRS system. In addition, these two proteins also appear to be affected by the virulence factor, gelatinase (GelE). GelE is a secreted zinc metalloprotease known to impact various cellular functions by post- translational modification of protein substrates. The overall objective of this work was to understand how GelE cleavage of secreted proteins, specifically AtlA and SalB, changes their function. Herein, I discovered that GelE modifies both AtlA and SalB. As visualized by Western blot analysis …
Characterization Of The Ato Gene Family In Alternative Carbon Metabolism, Heather A. Danhof
Characterization Of The Ato Gene Family In Alternative Carbon Metabolism, Heather A. Danhof
Dissertations & Theses (Open Access)
As a commensal colonizer and opportunistic pathogen, Candida albicans is the most clinically important human associated fungus. Systemic infection carries an unacceptably high mortality rate of ~40% in the growing population of immunocompromised individuals. Macrophages are important innate immune cells that limit the niches in the human body in which C. albicans can persist through phagocytic removal. However, following phagocytosis C. albicans readily escapes from the immune cell by differentiating into filamentous hyphae, a process that should be inhibited in the normally acidic phagolysosome. We have shown that C. albicans induces germination by neutralizing the phagolysosome. To better understand this …
Insights Into Determinants That Contribute To Colonization, Virulence And Antibiotic Resistance In Enterococci, Maria Camila Montealegre
Insights Into Determinants That Contribute To Colonization, Virulence And Antibiotic Resistance In Enterococci, Maria Camila Montealegre
Dissertations & Theses (Open Access)
Enterococcus faecalis and Enterococcus faecium are increasingly common as causative agents of human infections, many of which are very difficult to treat due to multi-drug resistance. The work presented in the first part of this dissertation elucidates a mechanism for the regulation of pilus expression. I showed that ATT is the initiation codon of ebpA, the first gene of an operon that codes for the endocarditis and biofilm-associated pili (Ebp), a recognized virulence factor in E. faecalis. The presence of this rare start codon downregulates EbpA translation and protein levels, diminishing biofilm and binding abilities of …
Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller
Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller
Dissertations & Theses (Open Access)
The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H2O2. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H2O2 by itself is not a …
Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope, Trista M. Berry
Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope, Trista M. Berry
Dissertations & Theses (Open Access)
Many bacteria use Type IV Secretion Systems (T4SSs) to aid in pathogenesis by translocating virulence factors across the cell envelope and into eukaryotic cells. These systems are structurally and functionally diverse, but are often compared to the archetypal VirB/VirD4 T4SS of Agrobacterium tumefaciens. This system is composed of the VirD4 type IV coupling protein (T4CP) and 11 VirB subunits (VirB1-11) that assemble as the secretion channel and an extracellular pilus. The T4CP is an inner membrane ATPase that interacts with T4SS substrates and the secretion channel, and is thought to link substrates with the secretion channel and possibly energize …
Regulation Of The Candida Albicans Arginine Biosynthetic Pathway, Claudia Jimenez Lopez
Regulation Of The Candida Albicans Arginine Biosynthetic Pathway, Claudia Jimenez Lopez
Dissertations & Theses (Open Access)
Candida albicans is the most importan thuman-associatedfungus.It is a commensal microorganism but also an opportunistic pathogen able to cause superficial infections aswellaslife-threateninginfectionswhich are associated with a highmortalityrateof 50%. The interactions between C. albicans and the cells of the mammalian innate immune system, which confer the most important protecting mechanisms against disseminated infections, are very dynamic and determine the success of C. albicans as a pathogen. Transcriptional profiling has shown that phagocytosis of C. albicans by macrophages results primarily in the activation of alternative carbon metabolism pathways suggesting that the pathogen is exposed to a glucose poor environment. Changes in …
Characterization Of The Role(S) Of Env Protein Of Human Endogenous Retrovirus-K In Multiple Human Cancers, Ming Li
Dissertations & Theses (Open Access)
Human endogenous retroviruses (HERVs) are remnants from ancient retroviral infections, and most of them are inactive in normal tissues. One family of HERV, HERV-K, is found to be associated with multiple human cancers including breast cancer, pancreatic cancer and melanoma, but the causal relationship between HERV-K and cancer is still unclear. Increased expression of HERV-K in melanoma cells correlates with malignant transformation, while a serological response to HERV-K in breast cancer or melanoma patients correlates with survival probability. However, the mechanism behind these observations remains obscure. Our laboratory reported that anti-HERV-K envelope (Env) protein antibodies show antitumor potential in targeting …
Molecular And Genomic Based Insights Into The Evolution Of Enterococcus Faecium From Commensal To Hospital-Adapted Pathogen, Jessica R. Galloway-Pena
Molecular And Genomic Based Insights Into The Evolution Of Enterococcus Faecium From Commensal To Hospital-Adapted Pathogen, Jessica R. Galloway-Pena
Dissertations & Theses (Open Access)
The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, …
Regulation Of Toxin Synthesis By Clostridium Difficile, Charles Darkoh
Regulation Of Toxin Synthesis By Clostridium Difficile, Charles Darkoh
Dissertations & Theses (Open Access)
Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …
Control Of The Master Virulence Regulatory Gene Atxa In Bacillus Anthracis, Jennifer L. Dale
Control Of The Master Virulence Regulatory Gene Atxa In Bacillus Anthracis, Jennifer L. Dale
Dissertations & Theses (Open Access)
Transcription of the Bacillus anthracis structural genes for the anthrax toxin proteins and biosynthetic operon for capsule are positively regulated by AtxA, a transcription regulator with unique properties. Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. In batch culture, multiple signals impact atxA transcript levels, and the timing and steady state level of atxA expression is critical for optimal toxin and capsule synthesis. Despite the apparent complex control of atxA transcription, only one trans-acting protein, the transition state regulator AbrB, has been demonstrated …
Functional Characterization Of Atxa, The Bacillus Anthracis Virulence Regulator, Troy G. Hammerstrom
Functional Characterization Of Atxa, The Bacillus Anthracis Virulence Regulator, Troy G. Hammerstrom
Dissertations & Theses (Open Access)
Coordinated expression of virulence genes in Bacillus anthracis occurs via a multi-faceted signal transduction pathway that is dependent upon the AtxA protein. Intricate control of atxA gene transcription and AtxA protein function have become apparent from studies of AtxA-induced synthesis of the anthrax toxin proteins and the poly-D-glutamic acid capsule, two factors with important roles in B. anthracis pathogenesis. The amino-terminal region of the AtxA protein contains winged-helix (WH) and helix-turn-helix (HTH) motifs, structural features associated with DNA-binding. Using filter binding assays, I determined that AtxA interacted non-specifically at a low nanomolar affinity with a target promoter (Plef) …
Novel Mechanisms Of Antigen Processing That Enhance Bcg Vaccine Efficacy, Christopher R. Singh
Novel Mechanisms Of Antigen Processing That Enhance Bcg Vaccine Efficacy, Christopher R. Singh
Dissertations & Theses (Open Access)
Mycobacterium tuberculosis, the causative agent of tuberculosis, is the most lethal single infectious agent afflicting man today causing 2 million deaths per year. The World Health Organization recommends a vaccine as the best option to prevent this disease. The current vaccine, BCG, has a variable efficacy and does not protect adults. It is known that BCG vaccine becomes sequestered in special phagosome compartments of macrophages that do not fuse with lysosomes. Since lysosome fusion is necessary for peptide production and T cell priming leading to protective TH1 immunity, we hypothesized that vaccine efficacy is reduced and occurs perhaps …
Role Of Vitamin-D3 And Retinoic Acid In A Human Thp-1 Macrophage Model Of Mycobacterium Tuberculosis Infection, Jaymie L. Estrella
Role Of Vitamin-D3 And Retinoic Acid In A Human Thp-1 Macrophage Model Of Mycobacterium Tuberculosis Infection, Jaymie L. Estrella
Dissertations & Theses (Open Access)
Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited the
subsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb …
Characterization Of The Agrobacterium Tumefaciens Virb2 Pilin Of The Virb/D4 Type Iv Secretion System, Jennifer Kerr
Characterization Of The Agrobacterium Tumefaciens Virb2 Pilin Of The Virb/D4 Type Iv Secretion System, Jennifer Kerr
Dissertations & Theses (Open Access)
The Agrobacterium tumefaciens VirB/D4 type IV secretion system (T4SS) delivers oncogenic T-DNA and effector proteins to susceptible plant cells. This leads to the formation of tumors termed Crown Galls. The VirB/D4 T4SS is comprised of 12 subunits (VirB1 to VirB11 and VirD4), which assemble to form two structures, a secretion channel spanning the cell envelope and a T-pilus extending from the cell surface. In A. tumefaciens, the VirB2 pilin subunit is required for assembly of the secretion channel and is the main subunit of the T-pilus. The focus of this thesis is to define key reactions associated with the T4SS …
A Metagenomic Study Of The Tick Midgut, Daniel T. Yuan
A Metagenomic Study Of The Tick Midgut, Daniel T. Yuan
Dissertations & Theses (Open Access)
A Metagenomic Study of the Tick Midgut
Daniel Yuan, B.S.
Supervisory Professor : Steven J. Norris, Ph.D.
Southern tick–associated rash illness (STARI) or Master’s disease is a Lyme-like illness that occurs following bites by Amblyomma americanum, the lone-star tick. Clinical symptoms include a bull’s eye rash similar to the erythema migrans lesions of Lyme disease, as well as fever and joint pains. Lyme disease is caused by Borrelia burgdorferi and related spirochetes. However, B. burgdorferi has not been detected in STARI patients, or in ticks in the South Central U.S. The causative agent of STARI has not been identified, …
Molecular Basis Of Corynebacterium Diphtheriae Virulence And Infection In The Caenorhabditis Elegans Model Host, Melissa M. Broadway
Molecular Basis Of Corynebacterium Diphtheriae Virulence And Infection In The Caenorhabditis Elegans Model Host, Melissa M. Broadway
Dissertations & Theses (Open Access)
Corynebacterium diphtheriae is the causative agent of cutaneous and pharyngeal diphtheria in humans. While lethality is certainly caused by diphtheria toxin, corynebacterial colonization may primarily require proteinaceous fibers called pili, which mediate adherence to specific tissues. The type strain of C. diphtheriae possesses three distinct pilus structures, namely the SpaA, SpaD, and SpaH-type pili, which are encoded by three distinct pilus gene clusters. The pilus is assembled onto the bacterial peptidoglycan by a specific transpeptidase enzyme called sortase. Although the SpaA pili are shown to be specific for pharyngeal cells in vitro, little is known about functions of the three …