High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families

Lan Lan Zhong, Hang T.T. Phan, Cong Shen, Karina Doris Vihta, Anna E. Sheppard, Xi Huang, Kun Jiao Zeng, Hong Yu Li, Xue Fei Zhang, Sandip Patil, Derrick W. Crook, A. Sarah Walker, Yong Xing, Jia Lin Lin, Lian Qiang Feng, Yohei Doi, Yong Xia, Nicole Stoesser, Guo Bao Tian

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Background. mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug- resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1- positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1-positive 3GC-R strains. Methods. Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized. Results. Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1-positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1-positive 3GC-R Enterobacteriaceae (P < .001). mcr-1-positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1-positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1-associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/ human reservoirs. Conclusions. The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.

Original languageEnglish
Pages (from-to)676-685
Number of pages10
JournalClinical Infectious Diseases
Issue number5
Publication statusPublished - 03-2018


All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Zhong, L. L., Phan, H. T. T., Shen, C., Vihta, K. D., Sheppard, A. E., Huang, X., Zeng, K. J., Li, H. Y., Zhang, X. F., Patil, S., Crook, D. W., Walker, A. S., Xing, Y., Lin, J. L., Feng, L. Q., Doi, Y., Xia, Y., Stoesser, N., & Tian, G. B. (2018). High rates of human fecal carriage of mcr-1-positive multidrug-resistant enterobacteriaceae emerge in China in association with successful plasmid families. Clinical Infectious Diseases, 66(5), 676-685. https://doi.org/10.1093/cid/cix885