RT Journal Article SR Electronic T1 High rates of human faecal carriage of mcr-1-positive multi-drug resistant isolates emerge in China in association with successful plasmid families JF bioRxiv FD Cold Spring Harbor Laboratory SP 106575 DO 10.1101/106575 A1 Lan-Lan Zhong A1 Hang TT Phan A1 Xi Huang A1 Karina Doris-Vihta A1 Anna E Sheppard A1 Kun-Jiao Zeng A1 Hong-Yu Li A1 Xue-Fei Zhang A1 Sandip Patil A1 Yan-Fen Zhang A1 Cong Shen A1 Derrick W Crook A1 A Sarah Walker A1 Yong Xing A1 Qian-yi Chen A1 Jia-lin Lin A1 Lian-Qiang Feng A1 Yohei Doi A1 Nicole Stoesser A1 Guo-Bao Tian YR 2017 UL http://biorxiv.org/content/early/2017/02/07/106575.abstract AB Background mcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning, given colistin is frequently used as a treatment of last resort in multidrug-resistant Enterobacteriaceae infections. Reported rates of human mcr-1 gastrointestinal carriage have historically been low.Objectives To identify trends in human gastrointestinal carriage of mcr-1 positive and mcr-1-positive/cefotaxime-resistant Enterobacteriaceae in Guangzhou, China, 2011-2016, and investigate the genetic contexts of mcr-1 in a subset of mcr-1-positive/cefotaxime-resistant strains using whole genome sequencing (WGS).Methods Of 8,022 faecal samples collected, 497 (6.2%) were mcr-1- positive, and 182 (2.3%) mcr-1-positive/cefotaxime-resistant. Trends in carriage were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (Illumina), and genetic contexts of mcr-1 were characterised.Results We observed marked increases in mcr-1 (now ~30% prevalence) and more recent (since January 2014) increases in mcr-1-positive/third-generation cephalosporin-resistant Enterobacteriaceae human colonisation (p<0.001). Sub-cultured mcr-1-positive/third-generation cephalosporin-resistant isolates were commonly multi-drug resistant.WGS of 50 mcr-1/third-generation cephalosporin-resistant isolates (49 Escherichia coli; 1 Klebsiella pneumoniae) demonstrated bacterial strain diversity (39 E. coli sequence types); mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and loss of the mcr-1-associated insertion sequence ISApl1 in some plasmids. Significant sequence similarity with published mcr-1 plasmid sequences was consistent with spread amongst pig, chicken and human reservoirs.Conclusions The high positivity rate (~10%) of mcr-1 in multidrug-resistant E. coli colonising humans is a clinical threat; the diverse genetic mechanisms (strains/plasmids/insertion sequences) associated with mcr-1 have likely contributed to its dissemination, and will facilitate its persistence.