AUTHOR=Zhu Xiao-Qing , Liu Yi-Yun , Wu Renjie , Xun Haoliang , Sun Jian , Li Jian , Feng Yaoyu , Liu Jian-Hua 

TITLE=Impact of mcr-1 on the Development of High Level Colistin Resistance in Klebsiella pneumoniae and Escherichia coli

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.666782

DOI=10.3389/fmicb.2021.666782

ISSN=1664-302X

ABSTRACT=<p>Plasmid-mediated colistin resistance gene <italic>mcr-1</italic> generally confers low-level resistance. The purpose of this study was to investigate the impact of <italic>mcr-1</italic> on the development of high-level colistin resistance (HLCR) in <italic>Klebsiella pneumoniae</italic> and <italic>Escherichia coli</italic>. In this study, <italic>mcr-1</italic>-negative <italic>K. pneumoniae</italic> and <italic>E. coli</italic> strains and their corresponding <italic>mcr-1</italic>-positive transformants were used to generate HLCR mutants <italic>via</italic> multiple passages in the presence of increasing concentrations of colistin. We found that for <italic>K. pneumoniae</italic>, 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 <italic>mcr-1</italic>-negative <italic>K. pneumoniae</italic> strains but only 16- to 256-fold for the <italic>mcr-1</italic>-harboring transformants. For <italic>E. coli</italic>, colistin MICs increased 4- to 64-folds, but only 2- to 16-fold for their <italic>mcr-1</italic>-harboring transformants. Notably, <italic>mcr-1</italic> improved the survival rates of both <italic>E. coli</italic> and <italic>K. pneumoniae</italic> strains when challenged with relatively high concentrations of colistin. In HLCR <italic>K. pneumoniae</italic> mutants, amino acid alterations predominately occurred in <italic>crrB</italic>, followed by <italic>phoQ</italic>, <italic>crrA</italic>, <italic>pmrB</italic>, <italic>mgrB</italic>, and <italic>phoP</italic>, while in <italic>E. coli</italic> mutants, genetic alterations were mostly occurred in <italic>pmrB</italic> and <italic>phoQ</italic>. Additionally, growth rate analyses showed that the coexistence of <italic>mcr-1</italic> and chromosomal mutations imposed a fitness burden on HLCR mutants of <italic>K. pneumoniae</italic>. In conclusion, HLCR was more likely to occur in <italic>K. pneumoniae</italic> strains than <italic>E. coli</italic> strains when exposed to colistin. The <italic>mcr-1</italic> gene could improve the survival rates of strains of both bacterial species but could not facilitate the evolution of high-level colistin resistance.</p>