中国血流感染相关产碳青霉烯酶肠杆菌的基因组及表型多样性——一项多中心流行病学、 微生物学和遗传学研究
郑焙文 , 徐浩 , 郭丽华 , 尉骁 , 嵇金如 , 应超群 , 陈云波 , 沈萍 , 韩慧明 , 黄晨 , 张舜天 , 吕涛 , 肖永红
工程(英文) ›› 2022, Vol. 12 ›› Issue (5) : 90 -100.
中国血流感染相关产碳青霉烯酶肠杆菌的基因组及表型多样性——一项多中心流行病学、 微生物学和遗传学研究
Genomic and Phenotypic Diversity of Carbapenemase-Producing Enterobacteriaceae Isolates from Bacteremia in China: A Multicenter Epidemiological, Microbiological, and Genetic Study
产碳青霉烯酶肠杆菌(CPE)是对全球公共卫生产生最严重威胁的病原菌之一。然而,血流感染(BSI)中CPE分离株的种群结构和遗传特征在很大程度上尚不清楚。为解决这一认知差距,将具有临床意义的由CPE引起的BSI 患者纳入本研究,并且于2014—2015 年在中国26 家哨点医院招募相关患者。对CPE分离株进行微生物学和基因组学表征,包括耐药谱、分子分型、系统发育特征以及碳青霉烯酶编码基因的遗传背景分析。在采集的2569 株BSI 相关肠杆菌中,发现42 株(1.6%)为碳青霉烯酶阳性。此外,对2242株大肠埃希菌、肺炎克雷伯菌、奇异变形杆菌和产酸克雷伯菌进行了产超广谱β-内酰胺酶(ESBL)检测试验,发现1111 株(49.6%)产ESBL菌株。全基因组测序分析显示,在收集的菌株中,产肺炎克雷伯菌碳青霉烯酶(KPC)-2 的ST11 型肺炎克雷伯菌和产新德里金属β-内酰胺酶(NDM)-5 的ST167 型大肠埃希菌在中国存在克隆扩散现象。质粒分析显示碳青霉烯酶编码基因位于多种类型的质粒上。此外,观察到在肺炎克雷伯菌分离株中生物膜形成相关的3 型菌毛簇基因和耶尔森菌素相关毒力基因的分离率较高。本研究证明了产ESBL菌株在中国BSI 分离株中的高流行率及CPE菌株在其中的广泛传播,凸显了上述两类病原菌在临床中产生的威胁。此外,本研究首次全面表征了BSI CPE分离株的基因组特征。强调未来需密切监测产KPC-2 的ST11 型肺炎克雷伯菌和产NDM-5 的ST167 型大肠埃希菌克隆在中国的播散情况。
Carbapenemase-producing Enterobacteriaceae (CPE) isolates are recognized as one of the most severe threats to public health. However, the population structure and genetic characteristics of CPE isolates among bloodstream infections (BSIs) are largely unknown. To address this knowledge gap, in this study, we included patients with clinically significant BSIs due to Enterobacterales isolates, recruited from 26 sentinel hospitals in China (2014–2015). CPE isolates were microbiologically and genomically characterized, including their susceptibility profiles, molecular typing, phylogenetic features, and genetic context analysis of carbapenemase-encoding genes. Of the 2569 BSI Enterobacterales isolates enrolled, 42 (1.6%) were carbapenemase-positive. Moreover, among the 2242 investigated isolates, 1111 (49.6%) extended-spectrum β-lactamase (ESBL)-producing isolates were identified in Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabilis), and Klebsiella oxytoca. Whole genome sequencing analysis showed the clonal spread of K. pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae sequence type 11 (ST11) and New Delhi metallo-β-lactamase (NDM)-5-producing E. coli ST167 in our collection. Plasmid analysis revealed that carbapenemase-encoding genes were located on multiple plasmids. A high prevalence of biofilm-encoding type 3 fimbriae clusters and yesiniabactin-associated genes was observed in K. pneumoniae isolates. This work demonstrates the high prevalence of ESBLs and the wide dissemination of CPE among BSI isolates in China, which represent real clinical threats. Moreover, our findings first illustrate a more comprehensive genome scenario of CPE isolates among BSIs. The clonal spread of KPC-2-producing K. pneumoniae ST11 and NDM-5-producing E. coli ST167 needs to be closely monitored.
碳青霉烯酶 / 产碳青霉烯酶肠杆菌 / 质粒介导 / 中国 / 产超广谱β-内酰胺酶
Carbapenemase / Carbapenemase-producing / Enterobacteriaceae / Plasmid-mediated / China / Extended-spectrum β-lactamase
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