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

Abstract

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, <i>mcr-1</i>, 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 <i>E. coli</i> K-12. Specifically, the impact of <i>mcr-1</i> on membrane permeability and antibiotic resistance of <i>E</i>. <i>coli</i> was assessed by constructing an <i>mcr-1</i> deletion mutant and by a complementation study. The removal of the <i>mcr-1</i> gene from plasmid pHNSHP45 not only led to reduced resistance to colistin but also resulted in a significant change in the membrane permeability of <i>E. coli</i>. Unexpectedly, the removal of the <i>mcr-1</i> 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 <i>mcr-1</i> also resulted in decreased growth rate and changed the cellular morphology of <i>E. coli.</i> Collectively, our results revealed that the spread of <i>mcr-1-</i>carrying plasmids alters other physiological functions in addition to conferring colistin resistance.