Pre-existing chromosomal polymorphisms in pathogenic <i>E. coli</i> potentiate the evolution of resistance to a last-resort antibiotic.

ABSTRACT: Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a 'last line of defence' antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of Escherichia coli to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistan

SUBMITTER: Jangir PK 

PROVIDER: S-EPMC9363117 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature