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

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2019 Jun 11

PMID 31179218

Citations 17

Authors

Huimin Zhang

Wenhui Wei

Man Huang

Zeeshan Umar

Youjun Feng

Affiliations

Soon will be listed here.

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 to ) from the aquatic bacterium 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 . In summary, the finding suggests that the aquatic bacterium (and even its associated aquaculture) is a reservoir for MCR-4 mobile colistin resistance.

Citing Articles

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References

Gros M, Rodriguez-Mozaz S, Barcelo D . Rapid analysis of multiclass antibiotic residues and some of their metabolites in hospital, urban wastewater and river water by ultra-high-performance liquid chromatography coupled to quadrupole-linear ion trap tandem mass spectrometry. J Chromatogr A. 2013; 1292:173-88. DOI: 10.1016/j.chroma.2012.12.072. View

Ding S, Han X, Li J, Gao W, Chen Z, Feng Y . Discovery of multi-drug resistant, MCR-1 and ESBL-coproducing ST117 Escherichia coli from diseased chickens in northeast China. Sci Bull (Beijing). 2023; 63(16):1059-1066. DOI: 10.1016/j.scib.2018.07.017. View

Feng Y, Kumar R, Ravcheev D, Zhang H . Paracoccus denitrificans possesses two BioR homologs having a role in regulation of biotin metabolism. Microbiologyopen. 2015; 4(4):644-59. PMC: 4554459. DOI: 10.1002/mbo3.270. View

Cullen T, Trent M . A link between the assembly of flagella and lipooligosaccharide of the Gram-negative bacterium Campylobacter jejuni. Proc Natl Acad Sci U S A. 2010; 107(11):5160-5. PMC: 2841920. DOI: 10.1073/pnas.0913451107. View

Chavda B, Lv J, Hou M, Chavda K, Kreiswirth B, Feng Y . Coidentification of and in a Clinical Enterobacter cloacae Isolate from China. Antimicrob Agents Chemother. 2018; 62(10). PMC: 6153785. DOI: 10.1128/AAC.00649-18. View

Huang Y, Tang Y, Cheng J, Wu Z, Mao Y, Liu P . Genome Analysis of Multidrug-Resistant Isolated From Human Soft Tissue Sample. Front Pharmacol. 2018; 9:419. PMC: 5932639. DOI: 10.3389/fphar.2018.00419. View

Xu Y, Zhong L, Srinivas S, Sun J, Huang M, Paterson D . Spread of MCR-3 Colistin Resistance in China: An Epidemiological, Genomic and Mechanistic Study. EBioMedicine. 2018; 34:139-157. PMC: 6116419. DOI: 10.1016/j.ebiom.2018.07.027. View

Potron A, Poirel L, Nordmann P . Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in Shewanella xiamenensis. Antimicrob Agents Chemother. 2011; 55(9):4405-7. PMC: 3165332. DOI: 10.1128/AAC.00681-11. View

Zhang H, Hou M, Xu Y, Srinivas S, Huang M, Liu L . Action and mechanism of the colistin resistance enzyme MCR-4. Commun Biol. 2019; 2:36. PMC: 6347640. DOI: 10.1038/s42003-018-0278-1. View

10.

Xu Y, Wei W, Lei S, Lin J, Srinivas S, Feng Y . An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance. mBio. 2018; 9(2). PMC: 5893884. DOI: 10.1128/mBio.02317-17. View

11.

Dixon R, Chopra I . Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli. J Antimicrob Chemother. 1986; 18(5):557-63. DOI: 10.1093/jac/18.5.557. View

12.

Chen L, Zhang J, Wang J, Butaye P, Kelly P, Li M . Newly identified colistin resistance genes, mcr-4 and mcr-5, from upper and lower alimentary tract of pigs and poultry in China. PLoS One. 2018; 13(3):e0193957. PMC: 5851611. DOI: 10.1371/journal.pone.0193957. View

13.

Singh S, Pathak A, Kumar A, Rahman M, Singh A, Gonzalez-Zorn B . Emergence of Chromosome-Borne Colistin Resistance Gene in Clinical Isolates of Klebsiella pneumoniae from India. Antimicrob Agents Chemother. 2017; 62(2). PMC: 5786762. DOI: 10.1128/AAC.01885-17. View

14.

Coates K, Walsh T, Spencer J, Hinchliffe P . 1.12 Å resolution crystal structure of the catalytic domain of the plasmid-mediated colistin resistance determinant MCR-2. Acta Crystallogr F Struct Biol Commun. 2017; 73(Pt 8):443-449. PMC: 5544000. DOI: 10.1107/S2053230X17009669. View

15.

Zhang H, Wei W, Huang M, Umar Z, Feng Y . Definition of a Family of Nonmobile Colistin Resistance (NMCR-1) Determinants Suggests Aquatic Reservoirs for MCR-4. Adv Sci (Weinh). 2019; 6(11):1900038. PMC: 6548957. DOI: 10.1002/advs.201900038. View

16.

Wei W, Zhang Y, Gao R, Li J, Xu Y, Wang S . Crystal structure and acetylation of BioQ suggests a novel regulatory switch for biotin biosynthesis in Mycobacterium smegmatis. Mol Microbiol. 2018; 109(5):642-662. DOI: 10.1111/mmi.14066. View

17.

Sun J, Xu Y, Gao R, Lin J, Wei W, Srinivas S . Deciphering MCR-2 Colistin Resistance. mBio. 2017; 8(3). PMC: 5424208. DOI: 10.1128/mBio.00625-17. View

18.

Kieffer N, Nordmann P, Poirel L . Moraxella Species as Potential Sources of MCR-Like Polymyxin Resistance Determinants. Antimicrob Agents Chemother. 2017; 61(6). PMC: 5444148. DOI: 10.1128/AAC.00129-17. View

19.

Carretto E, Brovarone F, Nardini P, Russello G, Barbarini D, Pongolini S . Detection of positive S serovar Typhimurium in clinical isolates of human origin, Italy, October to November 2016. Euro Surveill. 2018; 23(2). PMC: 5770850. DOI: 10.2807/1560-7917.ES.2018.23.2.17-00821. View

20.

AbuOun M, Stubberfield E, Duggett N, Kirchner M, Dormer L, Nunez-Garcia J . mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2017; 72(10):2745-2749. PMC: 5890717. DOI: 10.1093/jac/dkx286. View