摘要
      2017年，中国大陆禁止将粘菌素作为食品生产动物的饲料添加剂，导致中国大肠杆菌运动型粘菌素耐药性（mcr-1）的流行率下降。鼠伤寒沙门氏菌及其单相1，4，[5]，12:i:-变体也是与mcr-1传播相关的主要物种；然而，关于mcr-1在沙门氏菌中的流行和传播的证据尚缺乏。本文对2009年至2019年从中国南方广东省腹泻患者粪便样本中回收的5354株沙门氏菌进行了粘菌素耐药性和mcr-1筛选，并基于全基因组测序（WGS）数据对mcr-1阳性菌株进行了表征。确定了粘菌素耐药性和mcr-1的相对较高的流行率（4.05%/4.50%），更重要的是，粘菌素耐药和mcr-1-阳性沙门氏菌分离株的流行趋势具有相似的动态特征，即两者均于2012年首次被检测到，并在2013年至2016年间迅速增加，随后自2017年以来急剧下降。WGS和系统发育分析表明，无论是在禁令之前还是之后，mcr-1的持久性和跨医院传播主要由特定分支中具有相似主链的IncHI2质粒和序列型34（ST34）沙门氏菌决定，这些质粒和序列类型34与IncHI2质体和临床上重要的抗微生物耐药性基因的高流行率有关，包括blaCTX-M-14-fosA3-oqxAB-floR基因型。我们的工作揭示了中国粘菌素禁令前后临床沙门氏菌中mcr-1的患病率的差异，而10年来，mcr-1在不同医院的传播与耐多药IncHI2质粒和ST34沙门氏菌密切相关。需要继续监测，以探索最近的禁令后mcr-1急剧下降的相关因素，并确定该禁令是否影响了医疗系统中传播的沙门氏菌中mcr-1的携带。
ABSTRACT
The banning of colistin as a feed additive for food-producing animals in mainland China in 2017 caused the decline in the prevalence of Escherichia coli-mobilized colistin resistance (mcr-1) in China. Salmonella Typhimurium and its monophasic 1,4,[5],12:i:- variants are also the main species associated with the spread of mcr-1; however, the evidence of the prevalence and transmission of mcr-1 among Salmonella is lacking. Herein, the 5,354 Salmonella isolates recovered from fecal samples of diarrheal patients in Guangdong, Southern China, from 2009 to 2019 were screened for colistin resistance and mcr-1, and mcr-1-positive isolates were characterized based on whole-genome sequencing (WGS) data. Relatively high prevalence rates of colistin resistance and mcr-1 (4.05%/4.50%) were identified, and more importantly, the prevalence trends of colistin-resistant and mcr-1-positive Salmonella isolates had a similar dynamic profile, i.e., both were first detected in 2012 and rapidly increased during 2013 to 2016, followed by a sharp decrease since 2017. WGS and phylogenetic analysis indicate that, whether before or after the ban, the persistence and cross-hospital transmission of mcr-1 are primarily determined by IncHI2 plasmids with similar backbones and sequence type 34 (ST34) Salmonella in specific clades that are associated with a high prevalence of IncHI2 plasmids and clinically important antimicrobial resistance genes, including blaCTX-M-14-fosA3-oqxAB-floR genotypes. Our work reveals the difference in the prevalence rate of mcr-1 in clinical Salmonella before and after the Chinese colistin ban, whereas mcr-1 transmission was closely linked to multidrug-resistant IncHI2 plasmid and ST34 Salmonella across diverse hospitals over 10 years. Continued surveillance is required to explore the factors related to a sharp decrease in mcr-1 after the recent ban and determine whether the ban has affected the carriage of mcr-1 in Salmonella circulating in the health care system.

https://journals.asm.org/doi/full/10.1128/spectrum.03119-22