MCR Expression Conferring Varied Fitness Costs on Host Bacteria and Affecting Bacteria Virulence.

Since the first report of the plasmid-mediated, colistin-resistant gene, , nine genes and their subvariants have been identified. The spreading scope of varies greatly, suggesting that may have different evolutionary advantages. Depending on MCR family phylogeny, is highly similar to and , and are highly similar to and . We compared the expression effects of MCR-1~5 on bacteria of common physiological background. The MCR-1-expressing strain showed better growth than did MCR-2~5-expressing strains in the presence of colistin. LIVE/DEAD staining analysis revealed that MCR-3~5 expression exerted more severe fitness burdens on bacteria than did MCR-1 and -2. Bacteria expressing MCRs except MCR-2 showed enhanced virulence with increased epithelial penetration ability determined by trans-well model ( < 0.05). Enhanced virulence was also observed in the model, which may have resulted from bacterial membrane damage and different levels of lipopolysaccharide (LPS) release due to MCR expression. Collectively, MCR-1-expressing strain showed the best survival advantage of MCR-1~5-expressing strains, which may partly explain the worldwide distribution of . Our results suggested that MCR expression may cause increased bacterial virulence, which is alarming, and further attention will be needed to focus on the control of infectious diseases caused by -carrying pathogens.