Clostridium innocuum is a significant vancomycin-resistant pathogen for extraintestinal clostridial infection
Clostridium innocuum is a significant vancomycin-resistant pathogen for extraintestinal clostridial infection
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DOI：
10.1016/j.cmi.2017.02.025
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发表时间：
2017-08-01
影响因子：
14.2
通讯作者：
Chiu, C. -H.
中科院分区：
文献类型：
--
作者：
Chia, J. -H.;Feng, Y.;Chiu, C. -H.
目的：肠外梭菌感染（EICI）是一种罕见但致命的疾病。传统的表型方法只能将许多梭菌种分配到属水平。方法：收集376株非重复梭状芽孢杆菌无菌分离株，进行基质辅助激光解吸/电离飞行时间（MALDI-TOF）生物分型分析和16S rRNA测序。测定患者的抗菌药物敏感性，评估患者的临床特征。通过基因组测序和基因分型对无毒梭菌分离株进行了鉴定。我们采用分子和细胞方法探讨了无芽梭菌的毒力和耐药机制。结果：无芽梭菌（Clostridium innocuum）是引起EICI的第二常见菌，仅次于产气荚膜梭菌（Clostridium perfringens）。所有梭状芽孢杆菌对克林霉素、甲硝唑、青霉素、哌拉西林和氨苄西林-舒巴坦均敏感，而无毒梭状芽孢杆菌对万古霉素均耐药。在24例由innocuum引起的EICI患者中，腹泻2例（8.3%），软组织感染3例（12.5%），阑尾炎6例（25%），休克和胃肠道穿孔4例（16.7%）。30天死亡率为16.7%。从不同地点分离的无头弧菌无法通过基因分型分离。无毒梭菌基因组中未发现已知的毒素基因，但该物种对上皮细胞具有细胞毒性。d -丙氨酸- d -丙氨酸连接酶、丙氨酸消旋酶和d -丙氨酰- d -丙氨酸羧肽酶是无烟菌万古霉素耐药的三个主要基因。结论：万古霉素耐药无毒梭菌是一种以前未被发现但很重要的EICI病因。基因组分析表明，该物种可以携带一种脂多糖样结构，这种结构与体外细胞毒性有关。(C) 2017年欧洲临床微生物学与传染病学会。Elsevier Ltd.出版。版权所有。
Objectives: Extra-intestinal clostridial infection (EICI) is rare but can be fatal. Traditional phenotypic methods can only assign many of the Clostridium species to the genus level.Methods: A total of 376 non-repetitive Clostridium isolates from sterile sites were collected and subjected to matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) Biotyper analysis and 16S rRNA sequencing. Antimicrobial susceptibility was determined, and clinical characteristics of the patients were assessed. Clostridium innocuum isolates were characterized by genome sequencing and genotyping. We used molecular and cellular methods to explore the virulence and resistance mechanisms of C. innocuum.Results: Clostridium innocuum was the second most common species to cause EICI, only next to Clostridium perfringens. All Clostridium isolates showed susceptibility to clindamycin, metronidazole, penicillin, piperacillin and ampicillin-sulbatam, while C. innocuum isolates were invariably resistant to vancomycin. Among 24 patients with EICI caused by C. innocuum, two (8.3%) had diarrhoea, three (12.5%) had soft-tissue infection, six (25%) had appendicitis and four (16.7%) each had shock and gastrointestinal perforation. The 30-day mortality was 16.7%. The C. innocuum isolated from different sites could not be separated from one another by genotyping. No known toxin genes were identified in the genome of C. innocuum but the species expressed cytotoxicity to epithelial cells. D-Alanine-D-alanine ligase, alanine racemase and D-alanyl-D-alanine carboxypeptidase are three main genes responsible for vancomycin resistance in C. innocuum.Conclusions: Vancomycin-resistant C. innocuum is a previously unrecognized, yet prominent, cause for EICI. Genome analysis showed that the species could carry a lipopolysaccharide-like structure that is associated with cytotoxicity to cells in vitro. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.