Work

Convergence of genetic variants in MCR-1 and O-antigen conferring polymyxin resistance and fitness cost

Year: 2025

Type: article

Abstract: OBJECTIVE: The emergence of multidrug-resistant bacteria alongside the extensive spread of opportunistic pathogens with a diversity of serotypes threatens public health. Fitness cost and morphological variation are hypothesised to result from O-antigen diversity and lipid A modification, whereas these reconfigurations within lipopolysaccharides (LPS) confer polymyxin resistance. METHODS: In this study, a multidrug-resistant Escherichia coli named EcE.CRE.COL was isolated from a patient undergoing therapeutic laparoscope for liver cancer. Antibiotic susceptibility was measured using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France), and whole-genome sequencing revealed a chromosome and three plasmids (namely pEcE.CRE.COL015, pEcE.CRE.COL016, and pEcE.CRE.COL032). Comparative genomics was then conducted to identify genetic determinants accounting for multi-drug resistance. RESULTS: and mcr-1, accounting for corresponding antimicrobial resistance. We consequently proposed an evolutionary pattern for the spread of mcr-1, demonstrating that transposon-like architecture could play a key role in the dissemination of polymyxin resistance driven by mcr-1. In addition, a novel serotype gene cluster related to defective O-antigen synthesis was determined, likely resulting from a genetic insertion. SDS-PAGE indicated LPS defectiveness within this isolate, suggesting a variable charge on the membrane surface of EcE.CRE.COL. CONCLUSIONS: was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.

Source: Journal of Global Antimicrobial Resistance

DOI: 10.1016/j.jgar.2025.10.005