Research Projects

Antimicrobial resistance is a growing global issue that requires improved surveillance, effective diagnostics, and controlled antibiotic use. However, there has been little progress in this area, with no new antibiotic class introduced in the past 40 years. To address this, alternative approaches to single antibiotic treatments, such as beta-lactam antibiotics and beta-lactamase inhibitors, are being tested for safety, mechanism of action, and effectiveness. However, little is known about the time it takes for resistance to evolve against these antimicrobials and the molecular mechanisms of resistance. This project proposes investigating these characteristics for five candidate approaches. It will evolve replicate populations of E. coli in the presence of single antimicrobials, identify genomic changes that may have led to observed resistance, and use phenotypic microarrays to investigate the collateral evolution of resistance/sensitivity to other antimicrobial substances. The outcomes of this project can help identify alternatives to antibiotics that show delayed evolution of resistance. Genome sequencing will identify the molecular mechanisms leading to resistance and predict the speed of resistance spread. Additionally, the project will check whether resistance to a particular antimicrobial is likely to be accompanied by resistance to other antimicrobial substances, as collateral evolution is an important driver of resistance evolution. The project will build a laboratory-based framework to test the long-term efficacy of any new antimicrobial of interest, which can be extended to other pathogenic model systems in the future. The knowledge of long-term effectiveness of any antimicrobial will be crucial in guiding the clinical use of that drug.