Biochemistry, Biophysics, and Structural Biology Commons^™

Mechanistic Insight Into Β-Lactamase Catalysis, Inhibitor Design And Resistance, Michael Trent Kemp

USF Tampa Graduate Theses and Dissertations

The emergence of antibiotic resistance and spread of Gram negative bacteria poses a very real health threat to the public. The main mode of resistance within Gram negative bacteria is the production of β-lactamase enzymes that catalyze the breakdown of β-lactam antibiotics through a hydrolysis mechanism. Once the β-lactam ring is hydrolyzed and opened, the drug loses its efficacy, which allows for the bacteria to grow and proliferate uninhibited. These β-lactamase enzymes are organized into four categories based on the Ambler classification, with classes A, C and D being denoted as serine-based β-lactamase enzymes. Class B is composed of metalloenzymes …

Rna Polymerase Binding Protein A (Rbpa) Regulation Of Mycobacteria Transcription And Sensitivity To Fidaxomicin, Jerome Prusa

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis is the causative agent of the disease tuberculosis (TB) and remains one of the deadliest microorganisms on the planet. The effort to eradicate M. tuberculosis would benefit from the development of novel therapeutics, which requires a detailed understanding of M. tuberculosis physiology. Like all living organisms, M. tuberculosis gene expression requires transcription. Transcription in the phylum Actinobacteria, which includes mycobacteria, is unique because it includes RNA Polymerase Binding Protein A (RbpA) that is essential in both M. tuberculosis and the nonpathogenic model organism Mycobacterium smegmatis. RbpA increases the housekeeping A and housekeeping like B interactions with the RNA …

The Role Of The Msaabcr Operon In Cell Wall Integrity And Programmed Cell Death During Biofilm Development, Bibek G C

Dissertations

Staphylococcus aureus is an important human pathogen in both community and health care settings. Biggest challenges with S. aureus as a pathogen is its ability to acquire antibiotic resistance and produce robust biofilms. In this work, we investigated the nature of the cell wall defect in the msaABCR operon mutant in the Mu50 (VISA) and USA300 LAC methicillin-resistant Staphylococcus aureus (MRSA) strains. Results showed that msaABCR-mutant cells had decreased cell wall thickness and cell wall crosslinking in both strains. These defects are most likely due to increased murein hydrolase activity and/or nonspecific processing of murein hydrolases mediated by increased …

Type I Topoisomerases As Potential Targets For Therapeutics, Ahmed Seddek

FIU Electronic Theses and Dissertations

DNA topoisomerases are universal enzymes that control the topological features of DNA in all forms of life. This study aims to find potential inhibitors of some of the DNA topoisomerases in bacteria and humans that can be developed into potential therapeutics.

The first aim of this study is to find potential inhibitors of bacterial topoisomerase I that can be developed into antibiotics. There is an urgent need to develop novel antibiotics to overcome the world-wide health crisis of antimicrobial resistance. Virtual screening and biochemical assays were combined to screen thousands of compounds for potential inhibitors of bacterial topoisomerase I. NSC76027 …

Characterizing Mab Cluster R Prophage Of Pathogen Mycobacterium Abscessus (Mab), Madeline Kimble

Honors College

Mycobacterium abscessus (Mab) is an emerging pathogen that can cause pulmonary, skin and disseminating infections. It is one of the most drug-resistant pathogens and infections typically result in high morbidity and mortality. Understanding mechanisms of antibiotic resistance is critical for developing more effective treatments. Prophage, integrated viral genomes, are known to contribute to bacterial virulence and antibiotic resistance, yet Mab prophages remain largely uncharacterized.My research aims to characterize the diversity of the novel cluster MabR prophage genomes. The Molloy lab has demonstrated that the prophage McProf increases mycobacterial resistance to antibiotics. Using the McProf prophage genome sequence, we probed the …

Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena

Legacy Theses & Dissertations (2009 - 2024)

Mycobacterium abscessus (Mab), a non-tuberculous environmental mycobacterium is one of the emerging pathogens. The number of Mab infections has doubled in the past decade. It is also an opportunistic pathogen usually infecting immunocompromised individuals and causing numerous skin and soft tissue infections. It commonly causes lung infections in people who are already infected with one or other lung infections such as tuberculosis. The treatment of Mab infections is difficult because of its intrinsic resistance to most of the antibiotics available. This project studies Rifampicin (RIF) resistance in Mab, as RIF is a well-established treatment for other mycobacterial infections including tuberculosis, …