PAS Domain-Containing Chemoreceptors Influence the Signal Sensing and Intestinal Colonization of Vibrio cholerae.

Bacterial chemotaxis is the phenomenon in which bacteria migrate toward a more favorable niche in response to chemical cues in the environment. The methyl-accepting chemotaxis proteins (MCPs) are the principal sensory receptors of the bacterial chemotaxis system. Aerotaxis is a special form of chemotaxis in which oxygen serves as the signaling molecule; the process is dependent on the aerotaxis receptors (Aer) containing the Per-Arnt-Sim (PAS) domain. Over 40 MCPs are annotated on the genome of Vibrio cholerae; however, little is known about their functions. We investigated six MCPs containing the PAS domain in V. cholerae El Tor C6706, namely aer2, aer3, aer4, aer5, aer6, and aer7. Deletion analyses of each aer homolog gene indicated that these Aer receptors are involved in aerotaxis, chemotaxis, biofilm formation, and intestinal colonization. Swarming motility assay indicated that the aer2 gene was responsible for sensing the oxygen gradient independent of the other five homologs. When bile salts and mucin were used as chemoattractants, each Aer receptor influenced the chemotaxis differently. Biofilm formation was enhanced by overexpression of the aer6 and aer7 genes. Moreover, deletion of the aer2 gene resulted in better bacterial colonization of the mutant in adult mice; however, virulence gene expression was unaffected. These data suggest distinct roles for different Aer homologs in V. cholerae physiology.

mcr-1-Mediated In Vitro Inhibition of Plasmid Transfer Is Reversed by the Intestinal Environment.

Colistin is regarded as an antibiotic of last resort against multidrug-resistant Gram-negative bacteria, including Klebsiella pneumoniae and Escherichia coli. Colistin resistance is acquired by microorganisms via chromosome-mediated mutations or plasmid-mediated mobile colistin resistance (mcr) gene, in which the transfer of mcr is the predominant factor underlying the spread of colistin resistance. However, the factors that are responsible for the spread of the mcr gene are still unclear. In this study, we observed that mcr-1 inhibited the transfer of the pHNSHP45 backbone in liquid mating. Similar inhibitory effect of mcr-1.6 and chromosomal mutant ΔmgrB 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 mcr-1-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.