IMSc Webinar

Drug concentration dependent dynamics of resistance evolution in bacterial populations

Suman Gaurab Das

University of Bern

The emergence of antibiotic resistance is a major clinical challenge of the present day. To understand and predict the phenomenon, one must be able to quantitatively describe the evolutionary paths leading to resistance acquisition. I will present our contribution to this problem in two parts. In the first part, I will introduce a model based on empirical dose-response curves in which a bacterial fitness landscape changes systematically with drug concentration. The model predicts that epistasis, i.e. the interaction between mutational effects, is maximized at intermediate drug concentration. Despite the high ruggedness of the landscapes, we find the unexpected property that all fitness peaks are accessible from the wild type regardless of the concentration. We further predict that resistance evolves in two distinct phases involving the interplay of two different phenotypes, the quantitative features of the phases being determined by the drug concentration. In the second part, I will discuss the repeatability of the fixation of resistance mutations, which is a first step towards understanding the predictability of antibiotic resistance evolution. I will show how a heavy-tailed distribution of the fitness effects of mutations makes the degree of repeatability a non-self-averaging random variable. By applying this to data on resistance to the drug cefotaxime, I will demonstrate that at high concentration of the drug, the repeatability of fixation depends on the identity of resistance mutations and cannot be determined from the distribution of fitness effects alone.


zoom.us/j/97239618248

Meeting ID: 972 3961 8248
Passcode: 588184