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Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China

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Abstract

MCR-1-positve Escherichia coli (MCRPEC) have been reported in humans worldwide; however, thus far, their prevalence is low and potential sources for human mcr-1 carriage have not yet been identified. Here, we analyse a nationwide epidemiological dataset on MCRPEC in humans throughout China and assess the factors associated with MCRPEC carriage using natural and national anthropogenic data. We identified 774 non-duplicate MCRPEC isolates from 774 stool samples collected from 5,159 healthy individuals in 30 provinces and municipalities in 2016, with a prevalence of MCRPEC ranging from 3.7 to 32.7% (average: 15.0%)—substantially higher than previously reported. MCRPEC carriage was associated with provincial regions, the production of sheep and freshwater aquaculture, annual consumption of total meat, pork and mutton, and daily intake of aquaculture products. MCRPEC was significantly more prevalent in provinces with higher aquaculture industries. Whole-genome sequencing analysis revealed that the MCRPEC isolates were clustered into four distinct lineages, two of which were dominant and harboured most of the MCRPEC isolates. The high prevalence of MCRPEC in the community poses a substantial risk for colistin usage in clinical practice and suggests the need for intestinal screening of mcr-1 carriers in intensive care units in Chinese hospitals. Furthermore, our data suggest that aquaculture is a significant reservoir of mcr-1.

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Fig. 1: MCRPEC prevalence among 30 provinces and municipalities in China.
Fig. 2: Mapped MCRPEC prevalence, precipitation and freshwater aquaculture production, and intake of animal products per province.
Fig. 3: Genetic relationships between the MCRPEC isolates.
Fig. 4: Distribution of phylogenetic group, Inc type, ARGs and VAGs among MCRPEC isolates from 30 provinces and municipalities in China.

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  • 03 August 2018

    An incorrect Reporting Summary was originally published with this Article; this has now been replaced with the correct file.

References

  1. Liu, Y. Y. et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161–168 (2016).

    Article  PubMed  Google Scholar 

  2. Wang, Y. et al. Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study. Lancet Infect. Dis. 17, 390–399 (2017).

    Article  CAS  PubMed  Google Scholar 

  3. Di Pilato, V. et al. mcr-1.2, a new mcr variant carried on a transferable plasmid from a colistin-resistant KPC carbapenemase-producing Klebsiella pneumoniae strain of sequence type 512. Antimicrob. Agents Chemother. 60, 5612–5615 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bai, L. et al. A novel disrupted mcr-1 gene and a lysogenized phage P1-like sequence detected from a large conjugative plasmid, cultured from a human atypical enteropathogenic Escherichia coli (aEPEC) recovered in China. J. Antimicrob. Chemother. 72, 1531–1533 (2017).

    CAS  PubMed  Google Scholar 

  5. Tijet, N. et al. Molecular characteristics of mcr-1-carrying plasmids and new mcr-1 variant recovered from polyclonal clinical Escherichia coli from Argentina and Canada. PLoS ONE 12, e0180347 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lu, X. et al. MCR-1.6, a new MCR variant carried by an IncP plasmid in a colistin-resistant Salmonella enterica serovar Typhimurium isolate from a healthy individual.Antimicrob. Agents Chemother. 61, e02632-16 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Poirel, L., Jayol, A. & Nordmann, P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin. Microbiol. Rev. 30, 557–596 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Walsh, T. R. & Wu, Y. N. China bans colistin as a feed additive for animals. Lancet Infect. Dis. 16, 1102–1103 (2016).

    Article  PubMed  Google Scholar 

  9. Schwarz, S. & Johnson, A. P. Transferable resistance to colistin: a new but old threat. J. Antimicrob. Chemother. 71, 2066–2070 (2016).

    Article  PubMed  Google Scholar 

  10. Wang, X. et al. Molecular epidemiology of colistin-resistant Enterobacteriaceae in inpatient and avian isolates from China: high prevalence of mcr-negative Klebsiella pneumoniae. Int. J. Antimicrob. Agents 50, 536–541 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Quan, J. et al. Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study. Lancet Infect. Dis. 17, 400–410 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. Terveer, E. M. et al. Prevalence of colistin resistance gene (mcr-1) containing Enterobacteriaceae in feces of patients attending a tertiary care hospital and detection of a mcr-1 containing, colistin susceptible E. coli. PLoS ONE 12, e0178598 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bi, Z. et al. Prevalence of the mcr-1 colistin resistance gene in extended-spectrum β-lactamase-producing Escherichia coli from human faecal samples collected in 2012 in rural villages in Shandong Province, China. Int. J. Antimicrob. Agents 49, 493–497 (2017).

    Article  CAS  PubMed  Google Scholar 

  14. Zhong, L. L. et al. High rates of human fecal carriage of mcr-1-positive multi-drug resistant Enterobacteriaceae isolates emerge in China in association with successful plasmid families.Clin. Infect. Dis. 66, 676–685 (2017).

    Article  PubMed Central  Google Scholar 

  15. Wang, Y. et al. Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production. Nat. Microbiol. 2, 16260 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Bernasconi, O. J. et al. Travelers can import colistin-resistant Enterobacteriaceae, including those possessing the plasmid-mediated mcr-1 gene. Antimicrob. Agents Chemother. 60, 5080–5084 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cabello, F. C., Godfrey, H. P., Buschmann, A. H. & Dolz, H. J. Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance. Lancet Infect. Dis. 16, e127–e133 (2016).

    Article  PubMed  Google Scholar 

  18. Cabello, F. C., Tomova, A., Ivanova, L. & Godfrey, H. P. Aquaculture and mcr colistin resistance determinants. mBio 8, e01229-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yao, C. S. et al. Geographical agglomeration characteristic and spatial evolution mechanism of aquaculture industry in China [article in Chinese]. Econ. Geogr. 36, 118–127 (2016).

    Google Scholar 

  20. Wu, C. et al. Rapid rise of the ESBL and mcr-1 genes in Escherichia coli of chicken origin in China, 2008–2014.Emerg. Microbes Infect. 7, 30 (2018).

    PubMed  PubMed Central  Google Scholar 

  21. Sato, H., Ouchi, M. & Koumi, J. Distribution of colistin sulfate in the body. Distribution and metabolism of orally administered colistin sulfate in chickens and pigs [article in Japenase]. Jpn J. Antibiot. 25, 239–245 (1972).

    Article  CAS  PubMed  Google Scholar 

  22. Rhouma, M. et al. Gastric stability and oral bioavailability of colistin sulfate in pigs challenged or not with Escherichia coli O149: F4 (K88). Res. Vet. Sci. 102, 173–181 (2015).

    Article  CAS  PubMed  Google Scholar 

  23. Li, J., Milne, R. W., Nation, R. L., Turnidge, J. D. & Coulthard, K. Stability of colistin and colistin methanesulfonate in aqueous media and plasma as determined by high-performance liquid chromatography. Antimicrob. Agents Chemother. 47, 1364–1370 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qiong, C. & Ji-min, W. Current situation and future trends of meat consumption in China [ariticle in Chinese]. Food Nutr. China 19, 43–47 (2013).

    Google Scholar 

  25. Zhou, H. W. et al. Occurrence of plasmid- and chromosome-carried mcr-1 in waterborne Enterobacteriaceae in China.Antimicrob. Agents Chemother. 61, e00017-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Fernandes, M. R. et al. Colistin-resistant mcr-1-positive Escherichia coli in public beaches, an infectious threat emerging in recreational waters.Antimicrob. Agents Chemother. 61, e00234-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hu, Y. Y. et al. Colistin-resistance gene mcr-1 in children’s gut flora.Int. J. Antimicrob. Agents 50, 593–597 (2017).

    Article  CAS  PubMed  Google Scholar 

  28. M100-S25: Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement (Clinical and Laboratory Standards Institute, 2015).

  29. Bankevich, A. et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 19, 455–477 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Inouye, M. et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 6, 90 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Treangen, T. J., Ondov, B. D., Koren, S. & Phillippy, A. M. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol. 15, 524 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Letunic, I. & Bork, P. Interactive tree of life (iTOL)v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 44, W242–W245 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cheng, L., Connor, T. R., Siren, J., Aanensen, D. M. & Corander, J. Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol. Biol. Evol. 30, 1224–1228 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Carattoli, A. et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob. Agents Chemother. 58, 3895–3903 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by grants from the National Key Research and Development Program of China (2018YFD0500300), National Natural Science Foundation of China (81661138002 and 81772250) and Medical Research Council grant DETER-XDRE-CHINA (MR/P007295/1).

Author information

Authors and Affiliations

Authors

Contributions

Yang Wang, R.Z. and J.S. designed the study. Y.S., H.Z., J.X., Y.H., L.Y., Q.S., Y.O., Yue Wang and B.S. collected the data. Y.S., Yang Wang, Yong Wang, H.Z., R.Z., Q.Z., C.W., B.S., Z.S., Z.W., S.W., Y.Wu, C.C., J.L., T.R.W. and J.S. analysed and interpreted the data. Yang Wang, R.Z., Y.S. and T.R.W. wrote the manuscript. All authors reviewed, revised and approved the final report.

Corresponding authors

Correspondence to Jianzhong Shen, Rong Zhang or Yang Wang.

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Supplementary information

Supplementary Information

Supplementary Figures 1–5, Supplementary Tables 4 and 5.

Reporting Summary

Supplementary Table 1

Prevalence of mcr-1-positive samples and corresponding selected isolates for sequencing from 30 provinces in China.

Supplementary Table 2

Precipitation and anthropogenic data of 30 provinces in China.

Supplementary Table 3

MIC profiles of MCRPEC.

Supplementary Table 6

Characterization of 287 sequenced mcr-1-positive E. coli isolates.

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Shen, Y., Zhou, H., Xu, J. et al. Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China. Nat Microbiol 3, 1054–1062 (2018). https://doi.org/10.1038/s41564-018-0205-8

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