A5090685514- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Biochemical and Structural Characterization
- Cystic Fibrosis Research Advances
- Antimicrobial Peptides and Activities
- Drug Transport and Resistance Mechanisms
- Phenothiazines and Benzothiazines Synthesis and Activities
- Tracheal and airway disorders
- Drug-Induced Adverse Reactions
- Radiopharmaceutical Chemistry and Applications
- Protein Hydrolysis and Bioactive Peptides
- Cellular Mechanics and Interactions
- Pneumonia and Respiratory Infections
- Coccidia and coccidiosis research
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
- Plant Pathogenic Bacteria Studies
- Escherichia coli research studies
- Cardiomyopathy and Myosin Studies
- Bacteriophages and microbial interactions
- Fungal and yeast genetics research
- Boron Compounds in Chemistry
University of Manchester
2024
University of Birmingham
2019-2023
St George's, University of London
2017-2020
University of Kent
2017
Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux encouraging strategy to restore the antibacterial activity antibiotics. Chlorpromazine and amitriptyline have been shown behave as inhibitors. However, their mode action poorly understood. Exposure Salmonella enterica serovar Typhimurium Escherichia coli chlorpromazine selected for mutations within genes encoding RamR MarR, regulators tripartite pump AcrAB-TolC. Further...
Abstract Resistance–nodulation–division efflux pumps play a key role in inherent and evolved multidrug resistance bacteria. AcrB, prototypical member of this protein family, extrudes wide range antimicrobial agents out Although high-resolution structures exist for its conformational fluctuations their putative function are largely unknown. Here, we determine these structural dynamics the presence substrates using hydrogen/deuterium exchange mass spectrometry, complemented by molecular...
In Enterobacteriales, the AcrAB-TolC efflux pump exports substrates, including antimicrobials, from cell. Overexpression of can occur after exposure to fluoroquinolones, leading multidrug resistance. The expression in Salmonella is primarily regulated by transcriptional activator RamA. However, other activators, such as MarA, SoxRS, and Rob, influence expression. This study determined whether overproduction or absence RamA influences mutation rate phenotype mutants selected enterica serovar...
The actin cytoskeleton is modulated by regulatory actin-binding proteins which fine-tune the dynamic properties of polymer to regulate function. One such protein tropomyosin (Tpm), a highly-conserved alpha-helical dimer stabilises and regulates interactions with other proteins. Temperature sensitive mutants Tpm are invaluable tools in study filament dependent processes, critical viability cell. Here we investigated molecular basis temperature sensitivity fission yeast fail undergo...
Abstract Background Efflux pump inhibitors (EPIs) offer an attractive therapeutic option when combined with existing classes. However, their optimal dosing strategies are unknown. Methods MICs of ciprofloxacin (CIP)+/−chlorpromazine, phenylalanine-arginine β naphthylamide (PAβN) and a developmental molecule MBX-4191 were determined the pharmacodynamics (PD) was studied in vitro model employing Escherichia coli MG1655 its isogenic MarR mutant (I1147). Exposure ranging experiments performed...
Abstract Background Pseudomonas aeruginosa is the dominant pathogen causing lung infections in people with both cystic fibrosis (CF) and bronchiectasis, associated poorer outcomes. Unlike CF, bronchiectasis has been a neglected disease. More extensive genomic studies of larger patient cohorts within sampling are needed to improve understanding evolutionary mechanisms underpinning P. guide novel improved treatments. Methods We have performed genome sequencing 2,854 isolates from 180 patients...
Abstract Resistance-nodulation-division (RND) efflux pumps play a key role in inherent and evolved multidrug-resistance (MDR) bacteria. AcrB is the prototypical member of RND family acts to recognise export wide range chemically distinct molecules out bacteria, conferring resistance variety antibiotics. Although high resolution structures exist for AcrB, its conformational fluctuations their putative function are largely unknown, preventing complete mechanistic understanding inhibition....