Dataset Information

Colistin Resistance Gene mcr-1 and Its Variant in Escherichia coli Isolates from Chickens in China.

ABSTRACT: The mcr-1 gene was detected in 5.11% (58/1136) of Escherichia coli isolates of chicken origin from 13 provinces in China. A novel mcr-1 variant, named mcr-1.3, encoding an Ile-to-Val functional variant of MCR-1 was identified in a sequence type 155 (ST155) strain. An mcr-1.3-containing IncI2 plasmid, pHeN867 (60,757 bp), was identified. The transfer of pHeN867 led to a 32-fold increase in the MIC of colistin in the recipient, exhibiting an effect on colistin resistance that was similar to that of mcr-1.

SUBMITTER: Yang YQ

PROVIDER: S-EPMC5404584 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Colistin Resistance Gene mcr-1 and Its Variant in Escherichia coli Isolates from Chickens in China.

Yang Yong-Qiang YQ Li Yun-Xia YX Song Tao T Yang Yan-Xian YX Jiang Wei W Zhang An-Yun AY Guo Xin-Yi XY Liu Bi-Hui BH Wang Yong-Xiang YX Lei Chang-Wei CW Xiang Rong R Wang Hong-Ning HN

Antimicrobial agents and chemotherapy 20170424 5

The mcr-1 gene was detected in 5.11% (58/1136) of Escherichia coli isolates of chicken origin from 13 provinces in China. A novel mcr-1 variant, named mcr-1.3, encoding an Ile-to-Val functional variant of MCR-1 was identified in a sequence type 155 (ST155) strain. An mcr-1.3-containing IncI2 plasmid, pHeN867 (60,757 bp), was identified. The transfer of pHeN867 led to a 32-fold increase in the MIC of colistin in the recipient, exhibiting an effect on colistin re ...[more]

PMID: 28242671

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Project description:Colistin is one of the last-resort antibiotics for infections caused by multidrug-resistant Gram-negative bacteria. However, the wide spread of novel plasmid-carrying colistin resistance genes mcr-1 and its variants substantially compromise colistin's therapeutic effectiveness and pose a severe danger to public health. To detect colistin-resistant microorganisms induced by mcr genes, rapid and reliable antibiotic susceptibility testing (AST) is imminently needed. In this study, we identified an RNA-based AST (RBAST) to discriminate between colistin-susceptible and mcr-1-mediated colistin-resistant bacteria. After short-time colistin treatment, RBAST can detect differentially expressed RNA biomarkers in bacteria. Those candidate mRNA biomarkers were successfully verified within colistin exposure temporal shifts, concentration shifts, and other mcr-1 variants. Furthermore, a group of clinical strains were effectively distinguished by using the RBAST approach during the 3-h test duration with over 93% accuracy. Taken together, our findings imply that certain mRNA transcripts produced in response to colistin treatment might be useful indicators for the development of fast AST for mcr-positive bacteria. IMPORTANCE The emergence and prevalence of mcr-1 and its variants in humans, animals, and the environment pose a global public health threat. There is a pressing urgency to develop rapid and accurate methods to identify MCR-positive colistin-resistant bacteria in the clinical samples, providing a basis for subsequent effective antibiotic treatment. Using the specific mRNA signatures, we develop an RNA-based antibiotic susceptibility testing (RBAST) for effectively distinguishing colistin-susceptible and mcr-1-mediated colistin-resistant strains. Meanwhile, the detection efficiency of these RNA biomarkers was evidenced in other mcr variants-carrying strains. By comparing with the traditional AST method, the RBAST method was verified to successfully characterize a set of clinical isolates during 3 h assay time with over 93% accuracy. Our study provides a feasible method for the rapid detection of colistin-resistant strains in clinical practice.

Project description:The mobile colistin resistance gene mcr-1 has attracted global attention, as it heralds the breach of polymyxins, one of the last-resort antibiotics for the treatment of severe clinical infections caused by multidrug-resistant Gram-negative bacteria. To date, six slightly different variants of mcr-1, and a second mobile colistin resistance gene, mcr-2, have been reported or annotated in the GenBank database. Here, we characterized a third mobile colistin resistance gene, mcr-3 The gene coexisted with 18 additional resistance determinants in the 261-kb IncHI2-type plasmid pWJ1 from porcine Escherichia colimcr-3 showed 45.0% and 47.0% nucleotide sequence identity to mcr-1 and mcr-2, respectively, while the deduced amino acid sequence of MCR-3 showed 99.8 to 100% and 75.6 to 94.8% identity to phosphoethanolamine transferases found in other Enterobacteriaceae species and in 10 Aeromonas species, respectively. pWJ1 was mobilized to an E. coli recipient by conjugation and contained a plasmid backbone similar to those of other mcr-1-carrying plasmids, such as pHNSHP45-2 from the original mcr-1-harboring E. coli strain. Moreover, a truncated transposon element, TnAs2, which was characterized only in Aeromonas salmonicida, was located upstream of mcr-3 in pWJ1. This ΔTnAs2-mcr-3 element was also identified in a shotgun genome sequence of a porcine E. coli isolate from Malaysia, a human Klebsiella pneumoniae isolate from Thailand, and a human Salmonella enterica serovar Typhimurium isolate from the United States. These results suggest the likelihood of a wide dissemination of the novel mobile colistin resistance gene mcr-3 among Enterobacteriaceae and aeromonads; the latter may act as a potential reservoir for mcr-3IMPORTANCE The emergence of the plasmid-mediated colistin resistance gene mcr-1 has attracted substantial attention worldwide. Here, we examined a colistin-resistant Escherichia coli isolate that was negative for both mcr-1 and mcr-2 and discovered a novel mobile colistin resistance gene, mcr-3 The amino acid sequence of MCR-3 aligned closely with phosphoethanolamine transferases from Enterobacteriaceae and Aeromonas species originating from both clinical infections and environmental samples collected in 12 countries on four continents. Due to the ubiquitous profile of aeromonads in the environment and the potential transfer of mcr-3 between Enterobacteriaceae and Aeromonas species, the wide spread of mcr-3 may be largely underestimated. As colistin has been and still is widely used in veterinary medicine and used at increasing frequencies in human medicine, the continuous monitoring of mobile colistin resistance determinants in colistin-resistant Gram-negative bacteria is imperative for understanding and tackling the dissemination of mcr genes in both the agricultural and health care sectors.

Project description:Père David's deer (Elaphurus davidianus or milu) is an endangered species, and the prevalence of antimicrobial resistance (AMR) such as mcr-1-positive strains among them has been unknown. In this study, we aimed to investigate the genomic characterizations of mcr-1-positive strains and provide insight into the dissemination of AMR in nature reserve settings. Sixty-seven mcr-1-positive Escherichia coli isolates from 97 fecal samples were identified by PCR and found resistant to colistin. The prevalence of ?-lactam resistance was very high, and there were 64 mcr-1-positive isolates containing ?-lactamase genes. Transconjugants of 66 mcr-1-positive isolates were acquired through conjugation experiments. PCR-based replicon typing (PBRT) showed that 44 strains harbored IncI2 mcr-1-bearing plasmids, eight strains harbored IncX4 mcr-1-carrying plasmids, and 14 strains harbored IncHI2 mcr-1-positive plasmids. Notably, mcr-1 was located in the chromosome of LD27-1. Clonal dissemination and horizontal dissemination of mcr-1 by plasmids coexist. We first report the prevalence of plasmid-mediated mcr-1 in E. coli from Père David's deer in China. mcr-1-bearing IncI2 plasmid was the most frequent plasmid type, and the first IncI2 plasmid harboring both bla CTX-M-132 and mcr-1 is characterized here. Our results support the implication of Père David's deer as a potential reservoir for MCR-1-producing E. coli IMPORTANCE The mcr-1 gene is widely reported around the world and has been identified on various plasmids with different replicon types. Resistance to the last-line antibiotic colistin mediated by mcr-1 still represents a threat to global public health. Père David's deer is a highly endangered species originating in China, and many deer are currently being raised in captivity for gradual reintroduction to the wild. If this species carries AMR bacteria, it will pose a potential threat to the environment. Therefore, research on the dissemination of mcr-1-positive E. coli from Père David's deer is of great significance. This is the first study to investigate the microbiological and genomic surveillance of MCR-1-producing bacteria colonized among Père David's deer in China, and we uncovered a high prevalence of MCR-1-producing E. coli The importance of constant surveillance for AMR bacteria in nature reserve settings is emphasized.

Dataset Information

Colistin Resistance Gene mcr-1 and Its Variant in Escherichia coli Isolates from Chickens in China.

Publications

Colistin Resistance Gene <i>mcr-1</i> and Its Variant in Escherichia coli Isolates from Chickens in China.

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