Results We investigated two mcr-1-carrying polymyxin-resistant Salmonella enterica serovar Typhimurium ST34 isolates, S61394 and S44712, from bloodstream and intestinal Salmonella infection of two child inpatients, respectively. The transferability of mcr-1-harbouring plasmids was verified by conjugation. Complete genome sequences of mcr-1-harbouring isolates were determined using the PacBio RS II platform. Methods Salmonella isolates from gastroenteritis and bacteraemia were screened using primers targeting mcr-1. Cases of infection with mcr-1-harbouring Salmonella in child inpatients have not been reported in China before. coli carrying mcr-3.5 in South Korea, which implies that mcr-3 variants may have already been widely spread in the pig industry.Ībstract Objectives Children are vulnerable to Salmonella infection due to their immature immune system. To the best of our knowledge, this is the first report of pathogenic E. Further, the mcr-3.5 encodes three amino acid substitutions compared with mcr-3.1. Besides, the isolates carried various virulence factors and demonstrated resistance to multiple antimicrobials, including β-lactams and quinolones. We identified isolates with similar pulsed-field gel electrophoresis patterns from diseased pigs in three farms. Multi-locus sequence typing analysis revealed eight previously reported sequence types (ST), including ST1, ST10, and ST42. The mcr-3.1 and mcr-3.5 genes were identified predominantly in IncHI2 and IncP plasmids, respectively. coli J53 recipient strain from more than 50% of the mcr-3-carrying isolates. The mcr-3 genes were characterized as mcr-3.1 in 15 isolates and mcr-3.5 in 2 isolates. coli isolates determined in this study (47 from cattle, 90 from pigs, and 48 from chicken), PCR amplification detected mcr-3 genes in 17 isolates predominantly from diseased pigs. Among a total of 185 colistin-resistant E. We examined the prevalence and molecular characteristics of mcr-3 carrying colistin-resistant Escherichia coli among cattle, pig, and chicken isolates in South Korea. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. Contact with the mcr-containing reservoirs, consumption of contaminated animal-/plant-based foods or water, international animal-/plant-based food trades and travel, are routes for transmission of MGCB.ĪbstractThe emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens.
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Transmission of mcr to/among environmental strains is clonally unrestricted. Genes encoding multi-/extensive-drug resistance and virulence are often co-located with mcr on plasmids in environmental isolates.
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Insertion sequences (IS) (especially ISApl1) located upstream or downstream of mcr, class 1–3 integrons, and transposons are other drivers of mcr in the environment. Different conjugative and non-conjugative plasmids form the backbones for mcr in these isolates, but mcr have also been integrated into the chromosome of some strains. These genes are harboured by Escherichia coli, Enterobacter, Klebsiella, Proteus, Salmonella, Citrobacter, Pseudomonas, Acinetobacter, Kluyvera, Aeromonas, Providencia, and Raulotella isolates.
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The mcr-1, mcr-2, mcr-3, mcr-5, mcr-7, and mcr-8 have been detected in isolates from and/or directly in environmental samples. Mcr-gene-containing bacteria (MGCB) have disseminated by horizontal/lateral transfer into diverse ecosystems, including aquatic, soil, botanical, wildlife, animal environment, and public places. Bacteria have mobilized mcr genes (mcr-1 to mcr-9). COL has been used in livestock for decades globally. The emergence and spread of mobile colistin (COL) resistance (mcr) genes jeopardize the efficacy of COL, a last resort antibiotic for treating deadly infections.