Medicine and Health Sciences Commons^™

Mechanism Of Antibiotic Permeability Through The Gram-Negative Bacterial Envelope, Olaniyi Alegun

Theses and Dissertations--Chemistry

The outer membrane of Gram-negative bacteria (GN) makes them distinct among superbugs that are associated with the development of antibiotic resistance. The outer membrane, and inner membrane, separated by the periplasm, form a double-membrane barrier to the entry of antibiotics into the cell. Several studies have been conducted to examine the role of outer membrane modifications such as porins, lipopolysaccharides, and efflux pumps on antibiotic resistance. However, there is a paucity of knowledge on how antibiotics behave in the periplasm, to gain access into their target region. My thesis focuses on understanding the mechanism of antibiotic permeability through the cellular …

Preliminary Findings Of A Study On The Practice Of Self-Medication Of Antibiotics Among The Practicing Nurses Of A Tertiary Care Hospital, Akbar Shoukat Ali, Rahim Jandani, Arwa A. Al-Qahtani, Abdulkarem A S. Alenzi

Department of Medicine

Objectives: Antibiotic resistance is indeed a global concern. It is of significant concern especially in the low-middle income countries because of the ease of accessibility, affordability, and absence of regulations pertaining to the dispensing of non-prescription antibiotics. This study aims to estimate the frequency and factors associated with the self-medication of antibiotics found among the practicing nurses.
Methods: We conducted a descriptive cross-sectional study at a tertiary care hospital in Karachi, Pakistan from July 2016 to August 2016.
Results: Of the 48 recruited nurses, 60.4% (29/48) were practicing self-medication of antibiotics. There were slightly more male nurses (17/29) than their …

Investigation Of The Biosynthesis Of The Nucleoside Antibiotic Sphaerimicin, Jonathan Overbay

Theses and Dissertations--Pharmacy

Antibiotic-resistance has become a widespread problem in the United States and across the globe. Meanwhile, new antibiotics are entering the clinic at an alarmingly low rate. Highly-modified nucleosides, a class of natural products often produced by actinobacteria, target MraY bacterial translocase I. MraY is a clinically unexploited enzyme target that is ubiquitous and essential to peptidoglycan cell wall biosynthesis. The nucleoside antibiotics known vary in efficacy and the functionalities contributing to improved activity is poorly understood. Sphaerimicin, a newly discovered modified nucleoside, has potent inhibitory activity with an IC50 of 13.65 nM against MraY. In general, sphaerimicin is primarily effective …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao

Scripps Senior Theses

In response to the growing rates of antibiotic resistance in human bacterial pathogens, this study explores the natural products involved in the defensive symbiosis between actinobacteria and fungus-growing ants to uncover new potential antibiotics. This study also seeks to understand the function of natural antibiotics in their ecological contexts, especially those involved in defensive symbioses. Defensive symbiosis can be a beneficial platform for discovering useful antibiotics, because antibiotics in these relationships must be able to selectively inhibit enemies without harming hosts, and are therefore likely more specific and less toxic. Pseudonocardia sp. associated with Trachymyrmex septentrionalis ants demonstrated antibiotic activity …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Antibiotic Resistance In Escherichia Coli Iron Transport Mutants, Madeline Brandt

Honors Projects

Studies previously completed on Escherichia coli mutants suggested the possibility of iron uptake as an influence on the antibiotic resistance seen in different strains. The research focused on the TonB energy transduction system and its contributions to efflux-mediated antibiotic resistance. To test the hypothesis that iron uptake has an influence on antibiotic resistance in Escherichia coli, the sensitivity to a variety of antibiotics was evaluated in strains of E. coli lacking genes that relate to the uptake of iron or the efflux system that is necessary for the uptake of iron. To test the efflux systems TolC and TonB …

Direction Of Aminoacylated Transfer Rnas Into Antibiotic Synthesis And Peptidoglycan-Mediated Antibiotic Resistance, Jennifer Shepherd, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Prokaryotic aminoacylated‐transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated‐tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross‐linkage or change in membrane permeability is often a prerequisite for high‐level antibiotic resistance. In Streptomycetes, aminoacylated‐tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated‐tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review.

Single Daily Dosing Ceftriaxone And Metronidazole Vs Standard Triple Antibiotic Regimen For Perforated Appendicitis In Children: A Prospective Randomized Trial., Shawn D. St Peter, Kuojen Tsao, Troy L. Spilde, G W. Holcomb Iii, Susan W. Sharp, J Patrick Murphy, Charles L. Snyder, Ronald J. Sharp, Walter S. Andrews, Daniel J. Ostlie

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Appendicitis is the most common emergency condition in children. Historically, a 3-drug regimen consisting of ampicillin, gentamicin, and clindamycin (AGC) has been used postoperatively for perforated appendicitis. A retrospective review at our institution has found single day dosing of ceftriaxone and metronidazole (CM) to be a more simple and cost-effective antibiotic strategy. Therefore, we performed a prospective, randomized trial to compare efficacy and cost-effectiveness of these 2 regimens.

METHODS: After internal review board approval (IRB no. 04 12-149), children found to have perforated appendicitis at appendectomy were randomized to either once daily dosing of CM (2 total doses per …

Monitoring Lys-TrnaLys Phosphatidylglycerol Transferase Activity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In some bacteria Lys-tRNA^Lys is used both in translation and for the specific addition of Lys to phosphatidylglycerol in the cytoplasmic membrane. This reaction is catalyzed by the membrane protein MprF, and the lysyl-phosphatidylglycerol formed contributes to the resistance of these bacteria to various cationic antibacterial molecules. Obtaining proteins and reconstituting an in vitro system mimicking membrane conditions is a major challenge to studying the function of membrane proteins, especially when labile substrates such as Lys-tRNA^Lys are required. Here we report methods to obtain a stable enriched membrane fraction containing MprF, and the techniques necessary to quantitatively monitor …