Dissemination of the mcr-1 colistin resistance gene

Hu, Yongfei; Liu, Fei; Lin, Ivan Y. C.; Gao, George F.; Zhu, Baoli

doi:10.1016/s1473-3099(15)00533-2

Cited by 132 publications

(90 citation statements)

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“…We were surprised to find that this new, emerging mobile ARG has been transferred to the healthy Chinese human gut microbiota through a potential food chain dissemination pathway (46), which is more likely the case for several other mobile ARGs that are shared between the animals and humans we observed in this study. In addition, mcr-1 is currently found in or circulated among E. coli, K. pneumoniae, and S. enterica, which supports our results that the mobile ARGs are exchanged most frequently among these three bacterial species ( Fig.…”

Section: Discussionmentioning

confidence: 72%

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

Yang

et al. 2016

Appl Environ Microbiol

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Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (>99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria. The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens. Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens. IMPORTANCEThe development of antibiotic resistance threatens our modern medical achievements. The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic. Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints. We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens. This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature.A ntibiotic resistance is a growing global threat to human public health, and the continuing emergence of drug-resistant bacteria has led to the potential for a postantibiotic era (1). Bacteria have evolved a dynamic array of antimicrobial resistance mechanisms to withstand antibiotic attacks, such as altering drug target(s), synthesizing drug-inactivating enzymes, changing cell membrane permeability, and exporting drugs via efflux pumps (2). A large number of antibiotic resistance genes (ARGs) involved in these resistance mechanisms have been discovered and are collected in various ARG databases, including ARG-ANOTT (3), CARD (4), ResFinder (5), and ARDB (6). Because antibiotic resistance can be endogenous or exogenous, ARGs are generally classified as intrins...

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Section: Discussionmentioning

confidence: 72%

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

Yang

et al. 2016

Appl Environ Microbiol

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189

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“…Second, many of the mcr-1-positive isolates identified coharbor resistance determinants corresponding to specific antibiotics used in veterinary medicine, such as the floR gene encoding resistance to florfenicol (19). Many studies showed the wide dissemination of mcr-1-positive E. coli isolates, mostly in animals (14,23). Finally, the IncX4-type plasmids that are often identified as supporting the mcr-1 gene were identified in enterobacterial strains recovered from pigs, regardless of the presence of mcr-1 (24,25).…”

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Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants

Kieffer

Nordmann

Poirel

2017

Antimicrob Agents Chemother

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Plasmid-mediated resistance to polymyxins mediated by the MCR-1/2 determinants has been reported in Enterobacteriaceae worldwide. Using PCR-based and cloning strategies, a series of Moraxella spp. were screened for mcr-like genes. Moraxella spp. that are mainly animal pathogens but may also be human pathogens were identified as potential reservoirs of mcr-like genes.KEYWORDS polymyxin, plasmid, resistance, reservoir, animal, MCR R esistance to polymyxins in Enterobacteriaceae results mostly from chromosomal mutations in genes involved in modification of lipopolysaccharide (LPS) (1, 2). In particular, it has been shown that mutations, truncations, or insertions into genes encoding LPS-modifying enzymes may be responsible for acquired resistance to polymyxins in Enterobacteriaceae (1, 3, 4), Acinetobacter baumannii, and Pseudomonas aeruginosa (1, 5). However, the plasmid-mediated polymyxin resistance determinant MCR-1 was recently found in Escherichia coli and Klebsiella pneumoniae isolates recovered from humans and animals in China (6). The mcr-1 gene has been reported worldwide in other enterobacterial genera, including Enterobacter, Salmonella, and Shigella (7-11). This resistance was identified in Enterobacteriaceae isolated from various animal species, including cattle, chicken, and pigs (12-14), and from river samples and vegetables (15).MCR-1 is a 541-amino-acid phosphoethanolamine transferase that adds phosphoethanolamine to the lipid A moiety of LPS, leading to a more cationic LPS structure and consequently to resistance to polymyxins (6). Recently, the MCR-2 protein (538 amino acids long, 81% amino acid identity with MCR-1) was identified in Belgium from colistin-resistant E. coli (16). Additionally, the MCR-1.2 and MCR-1.3 variants (both exhibiting single amino acid substitutions versus MCR-1) were identified in Italy and China, respectively (17,18). Several plasmid types carrying the mcr-1 gene, belonging to the IncI2, IncHI2, or IncX4 incompatibility groups, have been identified (8,10,12). In addition, the mcr-1.2 and mcr-2 genes were found on IncX4 plasmid scaffolds (16,17).It is often suggested that animals treated with polymyxins represent a significant reservoir of polymyxin-resistant Gram-negative isolates, particularly MCR-producing isolates (19). In fact, polymyxins are heavily used in veterinary medicine, and Europeans, particularly in Spain and Italy, have a high consumption of those antibiotics for food-producing animals (20). The frequent identification of MCR-1-producing isolates from animals further supports the hypothesis that the animal world might be the primary source of this resistance determinant.

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“…Since the first report of plasmid pHNSHP45 carrying the mcr-1 gene (1), numerous retrospective studies have been performed worldwide to investigate the presence of this specific gene in strains isolated from environmental samples, food animals, food, and humans (2)(3)(4)(5)(6)(7)(8)(9)(10)(11), and the earliest evidence for its presence dates back to the 1980s (12). The mcr-1 gene was recently found to be carried by different plasmid replicon types, such as IncI2, IncHI2, IncP, IncFIP, and IncX4 (4,(13)(14)(15).…”

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MCR-1.6, a New MCR Variant Carried by an IncP Plasmid in a Colistin-Resistant Salmonella enterica Serovar Typhimurium Isolate from a Healthy Individual

Lü

Luo

et al. 2017

Antimicrob Agents Chemother

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In this study, we report a novel mcr-1 gene variant, named mcr-1.6, carried by an IncP plasmid in a colistin-resistant Salmonella enterica serovar Typhimurium isolate from a healthy person. Compared with mcr-1, the mcr-1.6 gene contains two single-nucleotide polymorphisms, one of which results in an arginine to histidine variation (Arg536¡His). The plasmid carrying the mcr-1.6 gene was designated pMCR1.6_P053 and is similar to a recently discovered mcr-1-bearing plasmid found in Klebsiella pneumoniae.

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Dissemination of the mcr-1 colistin resistance gene

Abstract: Antimicrobials increase travelers' risk of colonization by extended-spectrum betalactamase-producing Enterobacteriaceae.

Cited by 132 publications

References 5 publications

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants

MCR-1.6, a New MCR Variant Carried by an IncP Plasmid in a Colistin-Resistant Salmonella enterica Serovar Typhimurium Isolate from a Healthy Individual

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