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Co-transfer of blaNDM-5 and mcr-1 by an IncX3–X4 hybrid plasmid in Escherichia coli

Nature Microbiology volume 1, Article number: 16176 (2016) Cite this article

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Abstract

Carbapenem and colistin are the last-resort antibiotics used for treating multidrug-resistant Gram-negative pathogens. Here, we report, for the first time, co-transfer of resistance to both classes of antibiotics by a mobile IncX3–X4 hybrid plasmid in an Escherichia coli isolate. Spread of such a plasmid is of great concern for clinical therapy, and heightened efforts are needed to control its dissemination.

Carbapenems are considered the last resort for treating multidrug-resistant Enterobacteriaceae, while colistin is a key antibiotic used for treating carbapenem-resistant pathogens. Recently, Yi-Yun Liu1 and colleagues described plasmid-mediated resistance to colistin conferred by the mcr-1 gene encoding a phosphoethanolamine transferase. Since then, mcr-1 has been increasingly reported in Enterobacteriaceae around the world2,3. Notably, the plasmid harbouring mcr-1 was identified in multidrug-resistant Enterobacteriaceae isolates, some of which even produced carbapenemase4–7, such as Klebsiella pneumoniae carbapenemase (KPC), Verona integron–encoded metallo-β-lactamase (VIM) or New Delhi metallo-β-lactamase (NDM). More recently, it was found that mcr-1 was co-transferred with blaCTX-M by a single plasmid8,9. However, mcr-1 has not been shown to co-transfer with a carbapenem resistance gene. IncX plasmids are considered to be narrow-host-range plasmids of Enterobacteriaceae, and include at least five subtypes, IncX1 to IncX5 (ref. 10). Members of this group have been found to carry a wide variety of resistance-associated genes. For example, IncX3 plasmids play a significant role in the spread of blaNDM, especially blaNDM-4-like variants11, while evidence is accumulating that IncX4 plasmids are associated with the dissemination of mcr-1 (refs 5,12). These examples illustrate the importance of IncX plasmids in the transmission of resistance to antibiotics of clinical significance. Here, we report a carbapenem- and colistin-resistant E. coli strain that harbours a hybrid IncX3–X4 plasmid mediating co-transfer of blaNDM-5 and mcr-1.

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Figure 1: Genetic features of pCQ02-121 and proposed models for its formation.

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Acknowledgements

This work was supported by the National Natural Science Foundation and Natural Science Foundation of Guangdong Province, China (U1201214), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (IRT13063), the Natural Science Foundation of Guangdong Province (S2012030006590) and the National Basic Research Program of China (2016YFC1200100).

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  1. Jian Sun and Run-Shi Yang: †These authors contributed equally to this work.

Authors and Affiliations

  1. National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, 510642, Guangzhou, China

    Jian Sun, Run-Shi Yang, Liang-Xing Fang, Jing Xia, Liang Li, Xiao-Yue Lv, Jia-Hong Duan, Xiao-Ping Liao & Ya-Hong Liu

  2. College of Veterinary Medicine, South China Agricultural University, 510642, Guangzhou, China

    Jian Sun, Run-Shi Yang, Liang-Xing Fang, Jing Xia, Liang Li, Xiao-Yue Lv, Jia-Hong Duan, Xiao-Ping Liao & Ya-Hong Liu

  3. Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, 50011, Iowa, USA

    Qijing Zhang

  4. Department of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, 310027, Zhejiang, China

    Youjun Feng

  5. Jiangsu Co-Innovation Centre for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China

    Ya-Hong Liu

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  1. Jian Sun
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Contributions

J.S., R.-S.Y., Q.Z., Y.F., X.-P.L. and Y.-H.L. designed the study and prepared the manuscript. R.-S.Y., L.-X.F., J.X., L.L., X.-Y.L. and J.-H.D. performed experiments. All authors discussed the results. J.S., R.-S.Y., Q.Z., Y.F., X.L. and Y.-H.L. analysed data. J.S., Q.Z., Y.F. and Y.-H.L. drafted this manuscript.

Corresponding authors

Correspondence to Xiao-Ping Liao or Ya-Hong Liu.

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The authors declare no competing financial interests.

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Supplementary information

Supplementary Figures 1-3, Supplementary Tables 1-2 (PDF 1331 kb)

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Sun, J., Yang, RS., Zhang, Q. et al. Co-transfer of blaNDM-5 and mcr-1 by an IncX3–X4 hybrid plasmid in Escherichia coli. Nat Microbiol 1, 16176 (2016). https://doi.org/10.1038/nmicrobiol.2016.176

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