Journal of global antimicrobial resistance · 2025
Convergence of genetic variants in MCR-1 and O-antigen conferring polymyxin resistance and fitness cost.
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Lu Jinfeng, Zhou Aiping, Wang Dongjiang, Wan Shuang, Yang Yuting, Lv Na, Li Jun, Wu Guoping
Аннотация
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: This isolate exhibited characteristic resistance to carbapenems and polymyxin. Interestingly, pEcE.CRE.COL015 and pEcE.CRE.COL032 were shown to harbour blaNDM-5 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: Collectively, the co-occurrence of plasmid-borne mcr-1 and blaNDM-5 was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.
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: This isolate exhibited characteristic resistance to carbapenems and polymyxin. Interestingly, pEcE.CRE.COL015 and pEcE.CRE.COL032 were shown to harbour blaNDM-5 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: Collectively, the co-occurrence of plasmid-borne mcr-1 and blaNDM-5 was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.