Shiga Toxin-Mediated Hemolytic Uremic Syndrome: Time to Change the Diagnostic Paradigm?
Shiga Toxin-Mediated Hemolytic Uremic Syndrome: Time to Change the Diagnostic Paradigm?
复制标题
DOI：
10.1371/journal.pone.0001024
复制
发表时间：
2007-10-10
期刊：
影响因子：
3.7
通讯作者：
Mellmann, Alexander
中科院分区：
文献类型：
--
作者：
Bielaszewska, Martina;Koeck, Robin;Mellmann, Alexander
背景溶血性尿毒综合征（Hemolytic uremic syndrome，HUS）是由肠出血性大肠杆菌（enterohemorrhagic Escherichia coli，EHEC）引起的一种急性溶血性尿毒综合征，其主要毒力因子为志贺毒素（Shiga toxin，stx）和粘附素（adhesin intimin，eae）。stx阴性/eae阳性E. HUS患者粪便中的大肠杆菌及其临床意义尚不清楚。方法/主要调查结果。1996年至2006年，我们寻找stx阴性/eae阳性的E.用eae探针对HUS患者粪便中的EHEC进行菌落印迹杂交，并与引起HUS的EHEC进行比较。stx阴性/eae阳性E.大肠埃希菌是唯一的病原体分离出粪便的43（5.5%）的787例HUS患者;另外440（55.9%）例患者排泄EHEC。大多数（90.7%）stx阴性/eae阳性分离株属于血清型O26：H11/NM（非运动型）、O 103：H2/NM、O 145：H28/NM和O 157：H7/NM，这也是肠出血性大肠杆菌中最常见的血清型。stx阴性分离株与相应血清型的EHEC具有非stx毒力和适应性基因，多位点序列分型结果表明，stx阴性分离株与相应血清型的EHEC聚为同一克隆复合体，表明其与EHEC的亲缘关系较近。结论/意义。在微生物分析时，类似于5%的HUS患者不再排出致病性EHEC，但确实排出在感染期间失去stx的EHEC的stx阴性衍生物。在这类患者中，使用目前仅检测stx或滋贺毒素的方法会遗漏HUS的EHEC病因;这会妨碍流行病学调查并导致不适当的临床管理。在维持HUS由滋贺毒素触发的范例的同时，我们的数据表明考虑病原体在感染期间的遗传变化以适应适当的诊断策略的必要性。
Background. Hemolytic uremic syndrome (HUS) is caused by enterohemorrhagic Escherichia coli (EHEC) which possess genes encoding Shiga toxin (stx), the major virulence factor, and adhesin intimin (eae). However, the frequency of stx-negative/eae-positive E. coli in stools of HUS patients and the clinical significance of such strains are unknown. Methodology/Principal Findings. Between 1996 and 2006, we sought stx-negative/eae-positive E. coli in stools of HUS patients using colony blot hybridization with the eae probe and compared the isolates to EHEC causing HUS. stx-negative/eae-positive E. coli were isolated as the only pathogens from stools of 43 (5.5%) of 787 HUS patients; additional 440 (55.9%) patients excreted EHEC. The majority (90.7%) of the stx-negative/eae-positive isolates belonged to serotypes O26: H11/NM (nonmotile), O103:H2/NM, O145:H28/NM, and O157:H7/NM, which were also the most frequent serotypes identified among EHEC. The stx-negative isolates shared non-stx virulence and fitness genes with EHEC of the corresponding serotypes and clustered with them into the same clonal complexes in multilocus sequence typing, demonstrating their close relatedness to EHEC. Conclusions/Significance. At the time of microbiological analysis, similar to 5% of HUS patients shed no longer the causative EHEC, but do excrete stx-negative derivatives of EHEC that lost stx during infection. In such patients, the EHEC etiology of HUS is missed using current methods detecting solely stx or Shiga toxin; this can hamper epidemiological investigations and lead to inappropriate clinical management. While maintaining the paradigm that HUS is triggered by Shiga toxin, our data demonstrate the necessity of considering genetic changes of the pathogen during infection to adapt appropriately diagnostic strategies.