| Summary: | Colistin is regarded as an antibiotic of last resort against multidrug-resistant Gram-negative bacteria, including <i>Klebsiella pneumoniae</i> and <i>Escherichia coli</i>. Colistin resistance is acquired by microorganisms via chromosome-mediated mutations or plasmid-mediated mobile colistin resistance (<i>mcr</i>) gene, in which the transfer of <i>mcr</i> is the predominant factor underlying the spread of colistin resistance. However, the factors that are responsible for the spread of the <i>mcr</i> gene are still unclear. In this study, we observed that <i>mcr-1</i> inhibited the transfer of the pHNSHP45 backbone in liquid mating. Similar inhibitory effect of <i>mcr-1.6</i> and chromosomal mutant Δ<i>mgrB</i> suggested that colistin resistance, acquired from either plasmid or chromosomal mutation, hindered the transfer of colistin resistance-related plasmid in vitro. Dual plasmid system further proved that co-existing plasmid transfer was reduced too. However, this inhibitory effect was reversed in vivo. Some factors in the gut, including bile salt and anaerobic conditions, could increase the transfer frequency of the <i>mcr-1</i>-containing plasmid. Our results demonstrated the potential risk for the spread of colistin resistance in the intestine, provide a scientific basis against the transmission of colistin resistance threat.
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