Beta-lactamase dependent and independent evolutionary paths to high-level ampicillin resistance

• DOI: 10.1038/s41467-024-49621-2
• Publication Date: 2024-06-25T17:03:01Z
• Authors: Rotem Gross; Idan Yelin; Viktória Lázár; Manoshi Sen Datta; Roy Kishony
• Keywords: Amp resistance; Efflux; Beta-lactamase

Abstract The incidence of beta-lactam resistance among clinical isolates is a major health concern. A key method to study the emergence antibiotic adaptive laboratory evolution. However, in case ampicillin, bacteria evolved settings do not recapitulate clinical-like levels, hindering efforts identify evolutionary paths and their dependency on genetic background. Here, we used Microbial Evolution Growth Arena (MEGA) plate select ampicillin-resistant Escherichia coli mutants with varying degrees resistance. Whole-genome sequencing resistant revealed that ampicillin was acquired via combination single-point mutations amplification gene encoding beta-lactamase AmpC. blocking AmpC-mediated latent pathways: strains deleted for ampC were able adapt through combinations changes genes involved multidrug efflux pumps, transcriptional regulators, porins. Our results reveal distinct mutations, accessible at large population sizes, can drive high-level even independently beta-lactamases.