Two Classes of DNA Gyrase Inhibitors Elicit Distinct Evolutionary Trajectories Toward Resistance in Gram-Negative Pathogens.

ABSTRACT: Comprehensive knowledge of mechanisms driving the acquisition of antimicrobial resistance is essential for the development of new drugs with minimized resistibility. To gain this knowledge, we combine experimental evolution in a continuous culturing device, the morbidostat, with whole genome sequencing of evolving cultures followed by characterization of drug-resistant isolates. Here, this approach was used to assess evolutionary dynamics of resistance acquisition against DNA gyrase/topoisomerase TriBE inhibitor GP6 in Escherichia coli and Acinetobacter baumannii. The evolution of GP6 resistance in both species was driven by a combination of two classes of mutational events: (i) amino acid substitutions near the ATP-binding site of the GyrB subunit of the DNA gyrase target; a

SUBMITTER: Leyn SA 

PROVIDER: S-EPMC10327078 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature