Discovery of multi-drug resistant, MCR-1 and ESBL-coproducing ST117 Escherichia coli from diseased chickens in northeast China

Polymyxins, a family of cationic antimicrobial peptides, are recognized as a last‐resort clinical option used in the treatment of lethal infections with carbapenem‐resistant pathogens. A growing body of mobile colistin resistance (MCR) determinants renders colistin ineffective in the clinical and human sectors, posing a challenge to human health and food security. However, the origin and reservoir of the MCR family enzymes is poorly understood. Herein, a new family of nonmobile colistin resistance (from nmcr‐1 to nmcr‐1.8 ) from the aquatic bacterium Shewanella is reported. NMCR‐1 (541aa) displays 62.78% identity to MCR‐4. Genetic and structural analyses reveal that NMCR‐1 shares a similar catalytic mechanism and functional motifs, both of which are required for MCR action and its resultant phenotypic resistance to polymyxin. Phylogeny and domain‐swapping demonstrate that NMCR‐1 is a progenitor of MCR‐4 rather than MCR‐1/2. Additionally, the experiment of bacterial growth and viability reveals that NMCR‐1 promotes fitness cost as MCR‐1/4 does in the recipient Escherichia coli . In summary, the finding suggests that the aquatic bacterium Shewanella (and even its associated aquaculture) is a reservoir for MCR‐4 mobile colistin resistance.

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confidence: 99%

Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4

et al. 2019

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“…[69] The diagram for 2D ligand-protein interaction was generated using LigPlot+ software. [70] Phylogenetic Analyses: The MCR family of colistin resistance enzymes was downloaded from GenBank database, which covers no less than five different subtypes (i.e., MCR-1, [9,12,71] MCR-2, [21,22] MCR-3, [23,24] MCR-4, [25][26][27]72] and MCR-5 [13,25,26,28] ). Each subtype involves an array of heterogeneous variants as recently stated.…”

Section: Methodsmentioning

confidence: 99%

“…Phylogenetic Analyses : The MCR family of colistin resistance enzymes was downloaded from GenBank database, which covers no less than five different subtypes (i.e., MCR‐1, MCR‐2, MCR‐3, MCR‐4, and MCR‐5). Each subtype involves an array of heterogeneous variants as recently stated .…”

Section: Methodsmentioning

confidence: 99%

A Genomic, Evolutionary, and Mechanistic Study of MCR‐5 Action Suggests Functional Unification across the MCR Family of Colistin Resistance

et al. 2019

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A growing number of mobile colistin resistance (MCR) proteins is threatening the renewed interest of colistin as a “last‐resort” defense against carbapenem‐resistant pathogens. Here, the comparative genomics of a large plasmid harboring mcr‐5 from Aeromonas hydrophila and the structural/functional perspectives of MCR‐5 action are reported. Whole genome sequencing has identified the loss of certain parts of the Tn 3 ‐type transposon typically associated with mcr‐5 , providing a clue toward its mobilization. Phylogeny of MCR‐5 suggests that it is distinct from the MCR‐1/2 sub‐lineage, but might share a common ancestor of MCR‐3/4. Domain‐swapping analysis of MCR‐5 elucidates that its two structural motifs (transmembrane domain and catalytic domain) are incompatible with its counterparts in MCR‐1/2. Like the rest of the MCR family, MCR‐5 exhibits a series of conservative features, including zinc‐dependent active sites, phosphatidylethanolamine‐binding cavity, and the mechanism of enzymatic action. In vitro and in vivo evidence that MCR‐5 catalyzes the addition of phosphoethanolamine to the suggestive 4′‐phosphate of lipid A moieties is integrated, and results in the consequent polymyxin resistance. In addition, MCR‐5 alleviates the colistin‐induced formation of reactive oxygen species in E. coli . Taken together, the finding suggests that a growing body of MCR family resistance enzymes are functionally unified.

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“…ST117, one of most common ST of APEC, is regarded as an emerging human pathogen [271]. Most importantly, its carriage of ESBL has been reported many times [272][273][274]. This is also observed in our study.…”

Section: Phylogenic Analysis Based On Snpssupporting

confidence: 85%

Whole genome sequencing analysis of antimicrobial resistant Escherichia coli : from food to human

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The main work of this study is to analyze antimicrobial resistant E. coli based on whole genome sequencing data. Three stages were included for isolates from different sources (ready-to-eat food, retail raw meats and human patients).At the first stage, a retrospective study for antimicrobial resistant E. coli in readyto-eat (RTE) food sold in retail food premises in Singapore was performed in collaboration with Environmental Health Institute under NEA. A total of 99 E. coli isolates from poultry-based dishes (n=77) and fish-based dishes (n=22) were obtained between 2009 and 2014 during the surveillance project. All the isolates were included for disk diffusion testing for antimicrobial susceptibility testing.Of the 99 isolates, 24 (24.2%) were resistant to at least one antimicrobial agent. These isolates were then subjected to broth microdilution testing against 33 antimicrobial agents, including β-lactams, aminoglycosides, tetracycline, fluoroquinolones and polymyxin E (colistin), to determine the minimum inhibitory concentration (MIC) of isolates. Whole genome sequence (WGS) was carried out on the strains in order to correlate resistant phenotypes to putative antimicrobial resistance-related genes. Of the 24 isolates, 15 (62.5%) were found to be resistant to three or more classes of antimicrobials and thus were defined as multi-drug resistant strains. Two isolates (8.3%) were confirmed as Extended-Spectrum β-lactamase (ESBL)-producing E. coli by double disk synergy test.Based on WGS data, online analysis tool ResFinder detected 7 classes of antimicrobial resistance genes and resistance-related chromosomal point mutations in 19 of the 24 E. coli isolates. By analyzing the WGS contigs using BLASTn and KmerFinder, ESBL genes and transferable colistin resistance gene mcr-1 (2/24) and mcr-5 (1/24) were determined to be located on plasmids, which could pose a greater risk of AMR transfer among bacteria. Mutations were detected in four isolates within genes previously shown to confer resistance to quinolones (gyrA and parE) and tetracycline (rrsB). Prediction of AMR using WGS data was evaluated for six antimicrobials including ampicillin, chloramphenicol, colistin, fluoroquinolones, tetracycline and trimethoprim. The evaluation indicates WGS-based genotype and phenotype showed high consistency, however, for some antimicrobial resistance whose mechanism is not totally clear yet (such as colistin), there is challenge for resistance gene detection.To have a better understanding of genetic environment and mobility of colistin resistance gene mcr-5.1, the isolates carrying mcr-5.1 were sequenced using long-read sequencing technology. The plasmid sequences were assembled into a closed circle using both long-read sequencing data and short-read sequencing data. The blasting result showed the closest plasmid sequence to pSGMCR103 in NCBI is plasmid pYD786-3 (accession number KU254580.1) with 77% query coverage and 99% identity, which was carried by one E. coli isolate from human urine in USA. They share antimicrobial resistanc...

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Discovery of multi-drug resistant, MCR-1 and ESBL-coproducing ST117 Escherichia coli from diseased chickens in northeast China

Cited by 14 publications

References 63 publications

Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4

Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4

A Genomic, Evolutionary, and Mechanistic Study of MCR‐5 Action Suggests Functional Unification across the MCR Family of Colistin Resistance

Whole genome sequencing analysis of antimicrobial resistant Escherichia coli : from food to human

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