Berlin 2024 – scientific programme

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BP: Fachverband Biologische Physik

BP 1: Systems and Network Biophysics

BP 1.4: Talk

Monday, March 18, 2024, 10:30–10:45, H 0112

Elucidating the genetic determinants of antibiotic resistance evolution — •Gabriela Petrungaro, Theresa Fink, and Tobias Bollenbach — Institute for Biological Physics, University of Cologne, Germany

Biological evolution of bacterial populations under strong antibiotic selection can quickly lead to resistant populations that pose a threat to public health. To understand the evolutionary dynamics that lead to resistance, a thorough statistical characterization of this stochastic process is needed, which requires many repeats of the same experiments under tightly controlled conditions. Here, we report the results of 864 parallel automated evolution experiments with tight feedback control of population size and selection pressure. We investigate how the genetic background of an initially susceptible population constrains its ability to evolve resistance. To this end, we systematically compared 258 Escherichia coli strains that initially differ in single gene-deletions and evolve for two to three weeks under three clinically relevant antibiotics, one at a time. We find that evolution is highly parallel at the phenotypic and genotypic level, but the degree of parallelism varies among antibiotics. The evolutionary paths to resistance can be rationalized as biased random walks on a fitness landscape in genotype space. We find that certain gene deletions drastically alter these evolutionary paths, making new fitness peaks accessible and hampering others. Our results contribute to the understanding of repeatability in the evolution of antibiotic resistance and to the identification of possible targets for strategies to combat resistance.

Keywords: Antibiotic resistance; Evolutionary dynamics; Parallel biological evolution; Stochasticity of evolution; Fitness landscape