[Canceled] PME Special Seminar - Erdal Toprak

Molecular Evolution of Extended-Spectrum Beta-Lactamases and Non-Canonical Survival Strategies of Bacteria Under Beta-Lactam Treatment

In the first part of my talk, I will summarize our recent unpublished work, in which we systematically investigated the molecular evolution of extended-spectrum beta-lactamases (ESBLs), shaped by epistatic interactions between resistance-conferring mutations. Analyzing epistatic interactions both quantitatively and qualitatively using unsupervised and supervised deep learning models, we demonstrate how evolutionary trajectories leading to ESBLs are largely influenced by high-order epistatic interactions and evolutionary trade-offs.

In the second part of the talk, I will introduce a new mouse model we developed to study the evolution of antibiotic resistance I the mammalian gastrointestinal tract. Our study demonstrated that clinical isolates of Escherichia coli can survive clinically relevant beta-lactam treatment regimens without acquiring canonical resistance mechanisms, such as drug degradation, target modification or efflux.

Hosted by: Prof. Savas Tay