Impact of on the Development of High Level Colistin Resistance in and
Overview
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Plasmid-mediated colistin resistance gene generally confers low-level resistance. The purpose of this study was to investigate the impact of on the development of high-level colistin resistance (HLCR) in and . In this study, -negative and strains and their corresponding -positive transformants were used to generate HLCR mutants multiple passages in the presence of increasing concentrations of colistin. We found that for , HLCR mutants with minimum inhibitory concentrations (MICs) of colistin from 64 to 1,024 mg/L were generated. Colistin MICs increased 256- to 4,096-fold for -negative strains but only 16- to 256-fold for the -harboring transformants. For , colistin MICs increased 4- to 64-folds, but only 2- to 16-fold for their -harboring transformants. Notably, improved the survival rates of both and strains when challenged with relatively high concentrations of colistin. In HLCR mutants, amino acid alterations predominately occurred in , followed by , , , , and , while in mutants, genetic alterations were mostly occurred in and . Additionally, growth rate analyses showed that the coexistence of and chromosomal mutations imposed a fitness burden on HLCR mutants of . In conclusion, HLCR was more likely to occur in strains than strains when exposed to colistin. The gene could improve the survival rates of strains of both bacterial species but could not facilitate the evolution of high-level colistin resistance.
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