Mcr Expression Conferring Varied Fitness Costs On Host Bacteria And Affecting Bacteria Virulence

Since the first report of the plasmid-mediated, colistin-resistant gene, mcr-1, nine mcr genes and their subvariants have been identified. The spreading scope of mcr-1 similar to 10 varies greatly, suggesting that mcr-1 similar to 10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly similar to mcr-1 and -2, and mcr-7 similar to 10 are highly similar to mcr-3 and -4. We compared the expression effects of MCR-1 similar to 5 on bacteria of common physiological background. The MCR-1-expressing strain showed better growth than did MCR-2 similar to 5-expressing strains in the presence of colistin. LIVE/DEAD staining analysis revealed that MCR-3 similar to 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 (p < 0.05). Enhanced virulence was also observed in the Galleria mellonella 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 similar to 5-expressing strains, which may partly explain the worldwide distribution of mcr-1. 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 mcr-carrying pathogens.