High-throughput method characterizes hundreds of previously unknown antibiotic resistance mutations.

ABSTRACT: A fundamental obstacle to tackling the antimicrobial resistance crisis is identifying mutations that lead to resistance in a given genomic background and environment. We present a high-throughput technique - Quantitative Mutational Scan sequencing (QMS-seq) - that enables quantitative comparison of which genes are under antibiotic selection and captures how genetic background influences resistance evolution. We compare four E. coli strains exposed to ciprofloxacin, cycloserine, or nitrofurantoin and identify 812 resistance mutations, many in genes and regulatory regions not previously associated with resistance. We find that multi-drug and antibiotic-specific resistance are acquired through categorically different types of mutations, and that minor genotypic differences significantly influ

SUBMITTER: Jago MJ 

PROVIDER: S-EPMC11742677 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature