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Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing based molecular epidemiological study

By Cong Shen, Lan-Lan Zhong, Yongqiang Yang, Yohei Doi, David L. Paterson, Nicole Stoesser, Furong Ma, Mohamed Abd El-Gawad El-Sayed Ahmed, Siyuan Feng, Songying Huang, Hong-Yu Li, Xi Huang, Xin Wen, Zihan Zhao, Minmin Lin, Guanping Chen, Wanfei Liang, Yingjian Liang, Yong Xia, Min Dai, Ding-Qiang Chen, Liyan Zhang, Kang Liao, Guo-Bao Tian

Posted 03 Feb 2020
bioRxiv DOI: 10.1101/2020.02.03.923607 (published DOI: 10.1016/S2666-5247(20)30005-7)

Background: The global dissemination of colistin resistance encoded by mcr-1 has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence of mcr-1 in common pathogens, such as Escherichia coli, is of particular concern. Therefore, China banned the use of colistin in animal feed from May 1ST 2017. We investigated subsequent changes in mcr-1 prevalence, and the genomic epidemiology of mcr-1-positive Escherichia coli (MCRPEC). Methods: Sampling was conducted pre- (October-December 2016) and post-colistin ban (October-December, 2017 and 2018, respectively). 3675 non-duplicate pig fecal samples were collected from 14 provinces (66 farms) in China to determine intervention-related changes in mcr-1 prevalence. 15193 samples were collected from pigs, healthy human volunteers, colonized and infected hospital inpatients, food and the environment in Guangzhou, to characterize source-specific mcr-1 prevalence and the wider ecological impact of the ban. From these samples, 688 MCRPEC were analyzed with whole genome sequencing (WGS), plasmid conjugation and S1-PFGE/Southern blots to characterize associated genomic changes. Findings: After the ban, mcr-1 prevalence decreased significantly in national pig farms, from 45.0% (308/684 samples) in 2016, to 19.4% (274/1416) in 2018 (p<0.0001). This trend was mirrored in samples from most sources in Guangzhou (overall 19.2% [959/5003 samples] in 2016; 5.3% [238/4489] in 2018; p<0.0001). The population structure of MCRPEC was diverse (23 sequence clusters [SCs]); ST10 clonal complex isolates were predominant (247/688 [36%]). MCRPEC causing infection in hospitalized inpatients were genetically more distinct and appeared less affected by the ban. mcr-1 was predominantly found on plasmids (632/688 [92%]). Common mcr-1 plasmid types included IncX4, IncI2 and IncHI2 (502/656 [76.5%]); significant increases in IncI2-associated mcr-1 and a distinct lineage of mcr-1-associated IncHI2 were observed post-ban. Changes in the frequency of mcr-1-associated flanking sequences (ISApl1-negative MCRPEC), 63 core genome SNPs and 30 accessory genes were also significantly different after the ban, consistent with rapid genetic adaptation in response to changing selection pressures. Interpretation: A rapid, ecosystem-wide, decline in mcr-1 was observed after banning the use of colistin in animal feed, with associated genetic changes in MCRPEC. Genomic surveillance is key to assessing and monitoring stewardship interventions. Funding: National Natural Science Foundation of China. Keywords: Colistin; antimicrobial stewardship; intervention; mcr-1; Escherichia coli; genomic epidemiology

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