Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4
Abstract 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 clinic...
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doaj-8c787a4d2e7a439fa64e2eae1fcd5ee72020-11-24T22:05:14ZengWileyAdvanced Science2198-38442019-06-01611n/an/a10.1002/advs.201900038Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4Huimin Zhang0Wenhui Wei1Man Huang2Zeeshan Umar3Youjun Feng4Department of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaDepartment of Pathogen Biology & Microbiology and Department of General Intensive Care Unit of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310058 ChinaAbstract 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.https://doi.org/10.1002/advs.201900038aquatic environmentcolistinlipid Amarine bacteriaMCR‐4NMCR‐1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huimin Zhang Wenhui Wei Man Huang Zeeshan Umar Youjun Feng |
spellingShingle |
Huimin Zhang Wenhui Wei Man Huang Zeeshan Umar Youjun Feng Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 Advanced Science aquatic environment colistin lipid A marine bacteria MCR‐4 NMCR‐1 |
author_facet |
Huimin Zhang Wenhui Wei Man Huang Zeeshan Umar Youjun Feng |
author_sort |
Huimin Zhang |
title |
Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 |
title_short |
Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 |
title_full |
Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 |
title_fullStr |
Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 |
title_full_unstemmed |
Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4 |
title_sort |
definition of a family of nonmobile colistin resistance (nmcr‐1) determinants suggests aquatic reservoirs for mcr‐4 |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2019-06-01 |
description |
Abstract 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. |
topic |
aquatic environment colistin lipid A marine bacteria MCR‐4 NMCR‐1 |
url |
https://doi.org/10.1002/advs.201900038 |
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