Colistin Resistance Gene Mediates Cell Permeability and Resistance to Hydrophobic Antibiotics.

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