TY - JOUR T1 - High rates of human faecal carriage of <em>mcr-1-</em>positive multi-drug resistant isolates emerge in China in association with successful plasmid families JF - bioRxiv DO - 10.1101/106575 SP - 106575 AU - Lan-Lan Zhong AU - Hang TT Phan AU - Xi Huang AU - Karina Doris-Vihta AU - Anna E Sheppard AU - Kun-Jiao Zeng AU - Hong-Yu Li AU - Xue-Fei Zhang AU - Sandip Patil AU - Yan-Fen Zhang AU - Cong Shen AU - Derrick W Crook AU - A Sarah Walker AU - Yong Xing AU - Qian-yi Chen AU - Jia-lin Lin AU - Lian-Qiang Feng AU - Yohei Doi AU - Nicole Stoesser AU - Guo-Bao Tian Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/07/106575.abstract N2 - 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&lt;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. ER -