Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations.

ABSTRACT: Antibiotic-resistant pathogens are a major public health threat. A deeper understanding of how an antibiotic's mechanism of action influences the emergence of resistance would aid in the design of new drugs and help to preserve the effectiveness of existing ones. To this end, we developed a model that links bacterial population dynamics with antibiotic-target binding kinetics. Our approach allows us to derive mechanistic insights on drug activity from population-scale experimental data and to quantify the interplay between drug mechanism and resistance selection. We find that both bacteriostatic and bactericidal agents can be equally effective at suppressing the selection of resistant mutants, but that key determinants of resistance selection are the relationships between the number of dru

SUBMITTER: Hemez C 

PROVIDER: S-EPMC9463365 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature