Chen Kaichao, Yang Chen, Dong Ning, Xie Miaomiao, Ye Lianwei, Chan Edward Wai Chi, Chen Sheng
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, China.
mSystems. 2020 Dec 22;5(6):e01234-20. doi: 10.1128/mSystems.01234-20.
The incidence of ciprofloxacin resistance in has increased dramatically in the past decade. To track the evolutionary trend of ciprofloxacin resistance-encoding genetic elements during this period, we surveyed the prevalence of in food products in Shenzhen, China, during the period of 2012 to 2017 and performed whole-genome sequencing and genetic analysis of 566 ciprofloxacin-resistant clinical strains collected during this survey. We observed that target gene mutations have become much less common, with single mutation currently detectable in serovar Typhimurium only. Multiple plasmid-mediated quinolone resistance (PMQR) genes located in the chromosome and plasmids are now frequently detectable in ciprofloxacin-resistant strains of various serotypes. Among them, the gene was often harbored by multiple plasmids, with p10k-like plasmids being the most dominant. Importantly, p10k-like plasmids initially were not conjugative but became transmissible with the help of a helper plasmid. Ciprofloxacin resistance due to combined effect of carriage of the gene and other resistance mechanisms is common. In Typhimurium, carriage of is often associated with a single mutation; in other serotypes, combination of and other PMQR genes located in the chromosomal fragment or plasmid is observed. Another major mechanism of ciprofloxacin resistance, mainly observable in Derby, involves a chromosomal fragment harboring the elements. Intriguingly, this chromosomal fragment, flanked by IS, could form a circular intermediate and became transferrable. To conclude, the increase in the incidence of various PMQR mobile genetic elements and their interactions with other resistance mechanism contribute to a sharp increase in the prevalence of ciprofloxacin-resistant clinical strains in recent years. Resistance of nontyphoidal to fluoroquinolones such as ciprofloxacin is known to be mediated by target mutations. This study surveyed the prevalence of strains recovered from 2,989 food products in Shenzhen, China, during the period 2012 to 2017 and characterized the genetic features of several PMQR gene-bearing plasmids and ciprofloxacin resistance-encoding DNA fragments. The emergence of such genetic elements has caused a shift in the genetic location of ciprofloxacin resistance determinants from the chromosomal mutations to various mobile genetic elements. The distribution of these PMQR plasmids showed that they exhibited high serotype specificity, except for the p10k-like plasmids, which can be widely detected and efficiently transmitted among strains of various serotypes by fusing to a new conjugative helper plasmid. The sharp increase in the prevalence of ciprofloxacin resistance in recent years may cause a predisposition to the emergence of multidrug-resistant strains and pose huge challenges to public health and infection control efforts.
在过去十年中，环丙沙星耐药性的发生率急剧上升。为了追踪这一时期环丙沙星耐药性编码遗传元件的进化趋势，我们调查了2012年至2017年期间中国深圳食品中该菌的流行情况，并对在此调查中收集的566株环丙沙星耐药临床菌株进行了全基因组测序和遗传分析。我们观察到，靶基因突变变得不那么常见了，目前仅在鼠伤寒血清型中可检测到单基因突变。位于染色体和质粒上的多个质粒介导的喹诺酮耐药性（PMQR）基因现在在各种血清型的环丙沙星耐药菌株中经常可检测到。其中，qnr基因常常存在于多个质粒中，p10k样质粒最为常见。重要的是，p10k样质粒最初不具有接合性，但在辅助质粒的帮助下变得可传播。由于携带qnr基因和其他耐药机制的联合作用导致的环丙沙星耐药性很常见。在鼠伤寒沙门氏菌中，携带qnr基因通常与单个靶基因突变相关；在其他血清型中，观察到qnr基因与位于染色体片段或质粒上的其他PMQR基因的组合。环丙沙星耐药性的另一个主要机制，主要在德比沙门氏菌中观察到，涉及一个携带qnr元件的染色体片段。有趣的是，这个被IS侧翼包围的染色体片段可以形成一个环状中间体并变得可转移。总之，各种PMQR移动遗传元件发生率的增加及其与其他耐药机制的相互作用导致近年来环丙沙星耐药临床菌株的流行率急剧上升。已知非伤寒沙门氏菌对环丙沙星等氟喹诺酮类药物的耐药性是由靶基因突变介导的。本研究调查了2012年至2017年期间从中国深圳2989份食品中分离出的沙门氏菌菌株的流行情况，并对几种携带PMQR基因的质粒和环丙沙星耐药性编码DNA片段的遗传特征进行了表征。这些遗传元件的出现导致环丙沙星耐药决定因素的遗传位置从染色体突变转移到各种移动遗传元件。这些PMQR质粒的分布表明，除了p10k样质粒外，它们表现出高血清型特异性，p10k样质粒可以通过与新的接合辅助质粒融合而在各种血清型的沙门氏菌菌株中广泛检测到并有效传播。近年来环丙沙星耐药性流行率的急剧上升可能导致多重耐药沙门氏菌菌株的出现，并对公共卫生和感染控制工作构成巨大挑战。
