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

Abstract

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-1~10 varies greatly, suggesting that mcr-1~10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly similar to mcr-1 and -2, and mcr-7~10 are highly similar to mcr-3 and -4. 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 (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-1~5-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.

Multicentre evaluation of a selective isolation protocol for detection of mcr-positive E. coli and Salmonella spp. in food-producing animals and meat

“…A possible explanation may reside in a recent study analysing the fitness cost of bacteria carrying mcr‐1 to mcr‐5 , where the growth of mcr‐4 and mcr‐5 strains in broth culture was significantly inhibited in the log phase when colistin was added in the medium (Li et al . 2021).…”

“…To our knowledge, this is the first experiment using selective media to isolate colistin-resistant strains from meat samples, so it is difficult to state whether this difference in performance is due to the medium, the gene (mcr-4) or the bacteria (Salmonella). A possible explanation may reside in a recent study analysing the fitness cost of bacteria carrying mcr-1 to mcr-5, where the growth of mcr-4 and mcr-5 strains in broth culture was significantly inhibited in the log phase when colistin was added in the medium (Li et al 2021).…”

Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)

“…Antibiotic resistance mediated by acquiring mobile elements, including plasmids, imposes fitness costs on the bacterial host. In the absence of antibiotic pressure, sensitive strains can easily replace the resistant strains having an extra burden [ 86 , 87 ]. A recent study revealed that the expression of MCR-1 and MCR-3 has fitness cost on the first 50 generations of bacteria and that these genes and plasmids can persist over time, suggesting that the burden costs are alleviated through compensatory mutations [ 88 ].…”

“…Moreover, a study of the impact of diverse plasmids, harbouring COL resistance gene mcr-1 on host fitness, demonstrated that the IncI2, IncHI2 and IncX4 plasmid-carrying mcr-1 genes are stable and hardly affect bacterial growth, suggesting that most reported mcr-1 -plasmids belong primarily to these types [ 88 , 89 ]. Increased fitness or co-selection by other antimicrobials might contribute to the further dissemination of mcr-1 –positive plasmids [ 87 ].…”

Large-Scale Analysis of Fitness Cost of tet(X4)-Positive Plasmids in Escherichia coli

“…The plasmid stability of transconjugants was determined based on a previous study (Li et al, 2021b). Ten microliters of overnight seed cultures of the strains was inoculated into 10 ml antibiotic-free LB medium (1:1,000 ratio).…”