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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 /Â 30Â days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
03 August 2018
An incorrect Reporting Summary was originally published with this Article; this has now been replaced with the correct file.
References
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).
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).
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).
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).
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).
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).
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).
Walsh, T. R. & Wu, Y. N. China bans colistin as a feed additive for animals. Lancet Infect. Dis. 16, 1102–1103 (2016).
Schwarz, S. & Johnson, A. P. Transferable resistance to colistin: a new but old threat. J. Antimicrob. Chemother. 71, 2066–2070 (2016).
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).
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).
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).
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).
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).
Wang, Y. et al. Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production. Nat. Microbiol. 2, 16260 (2017).
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).
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).
Cabello, F. C., Tomova, A., Ivanova, L. & Godfrey, H. P. Aquaculture and mcr colistin resistance determinants. mBio 8, e01229-17 (2017).
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).
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).
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).
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).
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).
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).
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).
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).
Hu, Y. Y. et al. Colistin-resistance gene mcr-1 in children’s gut flora.Int. J. Antimicrob. Agents 50, 593–597 (2017).
M100-S25: Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement (Clinical and Laboratory Standards Institute, 2015).
Bankevich, A. et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 19, 455–477 (2012).
Inouye, M. et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 6, 90 (2014).
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).
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).
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).
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).
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
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
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Supplementary Information
Supplementary Figures 1–5, Supplementary Tables 4 and 5.
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.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41564-018-0205-8
This article is cited by
-
Low prevalence of colistin-resistant Escherichia coli from companion animals, China, 2018–2021
One Health Advances (2023)
-
Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings
The ISME Journal (2023)
-
Prevalence and transmission risk of colistin and multidrug resistance in long-distance coastal aquaculture
ISME Communications (2023)
-
Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers
European Journal of Clinical Microbiology & Infectious Diseases (2023)
-
Comparative genomic analyses of Polymyxin-resistant Enterobacteriaceae strains from China
BMC Genomics (2022)