Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease
Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease
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DOI：
10.1371/journal.ppat.1006238
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发表时间：
2017-03-01
期刊：
影响因子：
6.7
通讯作者：
Lewis, Amanda L.
中科院分区：
文献类型：
--
作者：
Gilbert, Nicole M.;O'Brien, Valerie P.;Lewis, Amanda L.
病原体通常无症状地存在于体内，对未知的触发因素做出反应而出现导致疾病。在膀胱，潜伏的细胞内大肠杆菌储存库被认为是反复尿路感染(RUTI)的可能来源，这是一个影响全球数百万女性的问题。然而，临床上看似合理的触发因素激活了这些储存库，目前尚不清楚。临床研究表明，女性阴道微生物区系的组成会影响她对Ruti的易感性，但这些联系背后的机制尚不清楚。一些证据表明，尿路经常暴露在阴道细菌中，包括阴道加德纳氏菌，这是一些女性阴道微生物群中的主要成员。使用小鼠模型，我们证明了膀胱暴露于阴道革兰氏菌会触发大肠杆菌从潜伏的膀胱库中排出，并增强由此产生的大肠杆菌Ruti导致危及生命的结果的可能性。短暂的阴道革兰氏吸虫暴露足以引起膀胱上皮细胞的凋亡和脱落，以及白介素1受体介导的肾脏损伤，这种损伤在阴道革兰氏吸虫从尿路中清除后仍持续存在。这些结果支持了对UTI发病机制的更广泛的看法，在UTI发病机制中，疾病可能是由短暂但强大的尿路暴露于阴道细菌而引起的，这些细菌本身就不是经典意义上的“尿路致病”。这一“隐蔽致病”模式可能适用于其他潜伏感染(如结核病)，或适用于目前被定义为非传染性疾病，因为常规培养未能检测到具有公认重要性的微生物。
Pathogens often inhabit the body asymptomatically, emerging to cause disease in response to unknown triggers. In the bladder, latent intracellular Escherichia coli reservoirs are regarded as likely origins of recurrent urinary tract infection (rUTI), a problem affecting millions of women worldwide. However, clinically plausible triggers that activate these reservoirs are unknown. Clinical studies suggest that the composition of a woman's vaginal microbiota influences her susceptibility to rUTI, but the mechanisms behind these associations are unclear. Several lines of evidence suggest that the urinary tract is routinely exposed to vaginal bacteria, including Gardnerella vaginalis, a dominant member of the vaginal microbiota in some women. Using a mouse model, we show that bladder exposure to G. vaginalis triggers E. coli egress from latent bladder reservoirs and enhances the potential for life-threatening outcomes of the resulting E. coli rUTI. Transient G. vaginalis exposures were sufficient to cause bladder epithelial apoptosis and exfoliation and interleukin-1-receptor- mediated kidney injury, which persisted after G. vaginalis clearance from the urinary tract. These results support a broader view of UTI pathogenesis in which disease can be driven by short-lived but powerful urinary tract exposures to vaginal bacteria that are themselves not "uropathogenic" in the classic sense. This " covert pathogenesis"paradigm may apply to other latent infections, ( e.g., tuberculosis), or for diseases currently defined as noninfectious because routine culture fails to detect microbes of recognized significance.