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Articles 1 - 13 of 13
Full-Text Articles in Medicine and Health Sciences
Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan
Molecular Mechanisms Of Antimicrobial Resistance In Multi-Drug Resistant Enterococci, Ayesha Khan
Dissertations & Theses (Open Access)
Antibiotic resistance is a major global public health threat. Enterococci are recalcitrant, nosocomial pathogens that can be intrinsically resistant to valuable antibiotics, like beta-lactams, or evolve resistance to all existing antimicrobials. The LiaFSR system regulates resistance to cell membrane (CM) stressors like daptomycin (DAP), a front-line drug for multi-drug resistant infections. DAP resistance (DAP-R) in E. faecalis is mediated by CM phospholipid alterations. Emergence of DAP-R often leads to b-lactam resensitization, a phenomenon called the seesaw effect. The molecular mechanism of DAP-R and the seesaw effect are unknown. Here we show that LiaX is a surface exposed protein whose C-terminal …
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 …
Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel
Assembly And Display Of Surface Proteins In Actinomyces Oris, Sara Siegel
Dissertations & Theses (Open Access)
Bacteria are an integral part of human health and disease. In the human host, dental plaques form as a result of up to 700 individual bacterial species colonizing oral surfaces and forming a multispecies biofilm. These biofilms are the cause of prevalent human diseases such as dental caries, gingivitis, and periodontitis. The microbes present in the oral biofilm are highly spatially and temporally structured and require a primary colonizing species to adhere to host tissue. As an important primary colonizer of the oral biofilm, the actinobacterium Actinomyces oris utilizes cell wall anchored proteins and glycoconjugates to initiate adherence to host …
Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez
Insights Into The Reactivation, Regulation And Essentiality Of Oxidative Protein Folding Pathways In Actinobacteria, Belkys Sanchez
Dissertations & Theses (Open Access)
Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence processes essential for bacterial physiology and pathogenicity. In the Gram-positive actinobacterial pathogens Actinomyces oris and Corynebacterium diphtheriae oxidative protein folding is catalyzed by the primary thiol-disulfide oxidoreductase MdbA. MdbA is required for assembly of adhesive pilus, which mediate receptor-dependent bacterial interactions, or coaggregation, in A. oris. In the first part of this dissertation, I identify components of the electron transport chain (ETC) required for …
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 Role Of The Pkm101-Encoded T4ss Outer Membrane Core Complex In Substrate Transfer, Pilus Biogenesis, And Recipient Cell Contact, Jay E. Gordon
Dissertations & Theses (Open Access)
The bacterial type IV secretion systems (T4SS) encoded on the Escherichia coli pKM101 and R388 conjugative plasmids and the Agrobacterium tumefaciens virB operon are composed of 12 subunits arranged in an architecturally similar fashion. Structural studies of the T4SS from R388 (TrwR388) highlighted the presence of a distinct outer membrane core complex (OMCC) and inner membrane complex (IMC) joined together by a central stalk. This thesis is focused on the development of the pKM101 model system and the role of an OMCC cap region formed by alpha helical antenna projections (AP) found in VirB10 and TraFpKM101. …
The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold
The Role Of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development, Jennifer L. Herold
Dissertations & Theses (Open Access)
Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of …
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 …
Regulators Of Bacterial Cell Division: Investigations Of Min Oscillation And Ftsa Activity, Jennifer R. Herricks
Regulators Of Bacterial Cell Division: Investigations Of Min Oscillation And Ftsa Activity, Jennifer R. Herricks
Dissertations & Theses (Open Access)
Cytokinesis is a fundamental process that is essential for bacterial proliferation. The cytokinetic machinery in bacteria is termed the “divisome”. The divisome is a complex of proteins that forms a ring at midcell over dividing nucleoids. In order for daughter cells to form, the divisome must constrict. As constriction occurs, two new cell poles are formed, one for each daughter cell. The first step in divisome formation is the assembly of FtsZ into a Z ring. The work presented in this dissertation focuses on two proteins that regulate the Z ring: MinD, which is a part of the Min system …
Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek
Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek
Dissertations & Theses (Open Access)
Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …
Development And Characterization Of An In Vitro Four-Species Anaerobic Dental Biofilm Model, Fernando Andrade
Development And Characterization Of An In Vitro Four-Species Anaerobic Dental Biofilm Model, Fernando Andrade
Dissertations & Theses (Open Access)
Dental caries is the most common chronic disease worldwide. It is characterized by the demineralization of tooth enamel caused by acid produced by cariogenic dental bacteria growing on tooth surfaces, termed bacterial biofilms. Cariogenesis is a complex biological process that is influence by multiple factors and is not attributed to a sole causative agent. Instead, caries is associated with multispecies microbial biofilm communities composed of some bacterial species that directly influence the development of a caries lesion and other species that are seemingly benign but must contribute to the community in an uncharacterized way. Clinical analysis of dental caries and …
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 …