德国研究人员23日在英国《柳叶刀传染病》期刊上报告说,本次德国肠出血性大肠杆菌疫情致病菌的菌株是10年前仅在德国现身过的一种大肠杆菌的克隆变种。这种病菌结合了肠出血性大肠杆菌和肠聚集性大肠杆菌的基因特性,因此具有更大危害性。
明斯特大学当天发布的新闻公报说,该校医学院卫生研究所所长卡希领导的研究小组分析了从德国17个城市共80名患者排泄物中分离出的菌株的遗传物质特性,发现所有这些菌株都属于血清型O104:H4型、序列型678型大肠杆菌。与此非常类似的大肠杆菌以往仅于2001年在德国两名患者身上出现过,这次却出人意料地在德国造成大流行。
研究小组还指出,本次暴发菌株都有与不同毒性相关的13个编码基因,包括肠出血性大肠杆菌常见的志贺毒素2的编码基因和与出血性腹泻相关的基因,还有与病菌黏附性相关的菌毛和黏附蛋白。
本次暴发菌株与2001年的分离菌株相比差别微小,主要是有了更多的抗生素耐药基因,同时又缺少了肠道聚集黏附大肠杆菌耐热肠毒素1基因。卡希认为,上述基因的增减是病原性大肠杆菌变异的常见现象。
卡希说,与肠聚集性大肠杆菌类似,本次暴发菌进入肠道后会成群聚集黏附在肠细胞上,形态如同“砖墙”一般。这时候病菌排出的志贺毒素往往会以迄今尚不明了的机理进入血液循环,并优先选择肾细胞和脑内皮细胞附着,造成肾和脑损坏,从而导致严重的溶血性尿毒综合征甚至使患者死亡。
卡希强调,目前这种病菌尚有许多未解之谜:是否仅仅是因为几种致病因素结合就使其有如此强的进攻性?到底需要多少病菌能造成感染?人类对这种病菌没有免疫能力是否是因为这种几乎是无中生有的病菌以前从未与人接触过?入侵人体之前,这种病菌又在何种群落生境中生存?
据德国负责汇总疫情的罗伯特科赫研究所23日公布的最新疫情通报,德国一个月来肠出血性大肠杆菌感染病例累计达3688例,其中患溶血性尿毒综合征的重症病例所占比例超过22%,远高于以往肠出血性大肠杆菌流行中不到10%的重症患者比例。截至22日,德国累计死亡患者已达42人。不过近两周来德国新增病例已明显减少。(生物谷Bioon.com)
生物谷推荐原文出处:
The Lancet doi:10.1016/S1473-3099(11)70165-7
Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study
Martina Bielaszewska MD , Alexander Mellmann MD , Wenlan Zhang MD , Robin Kck MD , Angelika Fruth PhD , Andreas Bauwens PhD , Georg Peters MD , Prof Helge Karch PhD
Background
In an ongoing outbreak of haemolytic uraemic syndrome and bloody diarrhoea caused by a virulent Escherichia coli strain O104:H4 in Germany (with some cases elsewhere in Europe and North America), 810 cases of the syndrome and 39 deaths have occurred since the beginning of May, 2011. We analysed virulence profiles and relevant phenotypes of outbreak isolates recovered in our laboratory.
Methods
We analysed stool samples from 80 patients that had been submitted to the National Consulting Laboratory for Haemolytic Uraemic Syndrome in Münster, Germany, between May 23 and June 2, 2011. Isolates were screened with standard PCR for virulence genes of Shiga-toxin-producing E coli and a newly developed multiplex PCR for characteristic features of the outbreak strain (rfbO104, fliCH4, stx2, and terD). Virulence profiles of the isolates were determined with PCR targeting typical virulence genes of Shiga-toxin-producing E coli and of other intestinal pathogenic E coli. We sequenced stx with Sanger sequencing and measured Shiga-toxin production, adherence to epithelial cells, and determined phylogeny and antimicrobial susceptibility.
Findings
All isolates were of the HUSEC041 clone (sequence type 678). All shared virulence profiles combining typical Shiga-toxin-producing E coli (stx2, iha, lpfO26, lpfO113) and enteroaggregative E coli (aggA, aggR, set1, pic, aap) loci and expressed phenotypes that define Shiga-toxin-producing E coli and enteroaggregative E coli, including production of Shiga toxing 2 and aggregative adherence to epithelial cells. Isolates additionally displayed an extended-spectrum β-lactamase phenotype absent in HUSEC041.
Interpretation
Augmented adherence of the strain to intestinal epithelium might facilitate systemic absorption of Shiga toxin and could explain the high progression to haemolytic uraemic syndrome. This outbreak demonstrates that blended virulence profiles in enteric pathogens, introduced into susceptible populations, can have extreme consequences for infected people.
Funding
German Federal Ministry of Education and Research, Network Zoonoses.