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Resistance to colistin, especially mobilized colistin resistance (mcr), is a serious threat to public health since it may catalyze a return of the “pre-antibiotic era”. Outer membrane vesicles (OMVs) play a role in antibiotic resistance in various ways. Currently, how OMVs participate in  mcr-1 -mediated colistin resistance has not been established. In this study, we showed that both OMVs from the  mcr-1  negative and positive  Escherichia coli  ( E. coli ) strains conferred dose-dependent protection from colistin. However, OMVs from the  mcr-1  positive strain conferred attenuated protection when compared to the OMVs of a  mcr-1  negative strain at the same concentration. The attenuated protective effect of OMVs was related to the reduced ability to absorb colistin from the environment, thus promoting the killing of colistin sensitive  E. coli  strains. Lipid A modified with phosphoethanolamine was presented in the OMVs of the  mcr-1  positive  E. coli  strain and resulted in decreased affinity to colistin and less protection. Meanwhile,  E. coli  strain carrying the  mcr-1  gene packed more unmodified lipid A in OMVs and kept more phosphoethanolamine modified lipid A in the bacterial cells. Our study provides a first glimpse of the role of OMVs in  mcr-1  -mediated colistin resistance.

The Attenuated Protective Effect of Outer Membrane Vesicles Produced by a mcr-1 Positive Strain on Colistin Sensitive Escherichia coli