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

Advanced Science - Tập 6 Số 11 - 2019
Huimin Zhang1,2, Wenhui Wei2, Man Huang2, Zeeshan Umar2, Youjun Feng2
1Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA
2Department of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China

Tóm tắt

AbstractPolymyxins, 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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Advanced Science

Tập 6 Số 11

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