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• W2934984844 abstract "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 Tn3-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." @default.
• W2934984844 created "2019-04-11" @default.
• W2934984844 creator A5005691727 @default.
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• W2934984844 date "2019-04-03" @default.
• W2934984844 modified "2023-10-17" @default.
• W2934984844 title "A Genomic, Evolutionary, and Mechanistic Study of MCR‐5 Action Suggests Functional Unification across the MCR Family of Colistin Resistance" @default.
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• W2934984844 doi "https://doi.org/10.1002/advs.201900034" @default.
• W2934984844 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6548960" @default.
• W2934984844 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31179217" @default.
• W2934984844 hasPublicationYear "2019" @default.
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