AUTHOR=Li Baiyuan , Yin Fang , Zhao Xuanyu , Guo Yunxue , Wang Weiquan , Wang Pengxia , Zhu Honghui , Yin Yeshi , Wang Xiaoxue 

TITLE=Colistin Resistance Gene mcr-1 Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.03015

DOI=10.3389/fmicb.2019.03015

ISSN=1664-302X

ABSTRACT=<p>Colistin is considered the last-resort antibiotic used to treat multidrug resistant bacteria-related infections. However, the discovery of the plasmid-mediated colistin resistance gene, <italic>mcr-1</italic>, threatens the clinical utility of colistin antibiotics. In this study, the physiological function of MCR-1, which encodes an LPS-modifying enzyme, was investigated in <italic>E. coli</italic> K-12. Specifically, the impact of <italic>mcr-1</italic> on membrane permeability and antibiotic resistance of <italic>E</italic>. <italic>coli</italic> was assessed by constructing an <italic>mcr-1</italic> deletion mutant and by a complementation study. The removal of the <italic>mcr-1</italic> gene from plasmid pHNSHP45 not only led to reduced resistance to colistin but also resulted in a significant change in the membrane permeability of <italic>E. coli</italic>. Unexpectedly, the removal of the <italic>mcr-1</italic> gene increased cell viability under high osmotic stress conditions (e.g., 7.0% NaCl) and led to increased resistance to hydrophobic antibiotics. Increased expression of <italic>mcr-1</italic> also resulted in decreased growth rate and changed the cellular morphology of <italic>E. coli.</italic> Collectively, our results revealed that the spread of <italic>mcr-1-</italic>carrying plasmids alters other physiological functions in addition to conferring colistin resistance.</p>