Department of Molecular Microbiology, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Infect Immun. 2010 May;78(5):1943-51. doi: 10.1128/IAI.01235-09. Epub 2010 Feb 22.
Staphylococcus saprophyticus, an obligate human pathogen, is the most common Gram-positive causative agent of urinary tract infection (UTI) in young, healthy women. Despite the clinical importance of S. saprophyticus, little is known about how it causes disease in the urinary tract or how the host responds to the infection. Here we established an in vivo model to study both host and bacterial factors contributing to S. saprophyticus UTI. Using this model, we show that S. saprophyticus preferentially infects C3H/HeN murine kidneys instead of the bladder, a trait observed for multiple clinical isolates. Bacterial persistence in the kidneys was observed in C3H/HeN mice but not in C57BL/6 mice, indicating that host factors strongly contribute to the ability of S. saprophyticus to cause UTI. Using C3H/HeN mice as a model, histologic and immunofluorescence analyses of infected tissues revealed that S. saprophyticus induced epithelial cell shedding in the bladder and an inflammatory response characterized by macrophage and neutrophil infiltration in the bladder and kidneys. The inflammatory response correlated with increased production of proinflammatory cytokines and chemokines in both the bladder and the kidneys. Finally, we observed that the putative S. saprophyticus virulence factors Ssp and SdrI were important for persistence, but not for initial colonization, in the murine urinary tract. Thus, we characterized both host and bacterial factors involved in progression of S. saprophyticus UTI, and we describe a useful model system for studying factors involved in the pathogenesis of this Gram-positive uropathogen.
解脲支原体是一种专性人类病原体，是年轻健康女性尿路感染（UTI）最常见的革兰阳性致病因子。尽管解脲支原体具有重要的临床意义，但人们对其在泌尿道引起疾病的机制以及宿主对感染的反应知之甚少。在这里，我们建立了一种体内模型来研究导致解脲支原体 UTI 的宿主和细菌因素。使用该模型，我们表明解脲支原体优先感染 C3H/HeN 鼠肾脏，而不是膀胱，这一特征在多个临床分离株中都观察到。在 C3H/HeN 小鼠中观察到细菌在肾脏中的持续存在，但在 C57BL/6 小鼠中则没有，这表明宿主因素强烈影响解脲支原体引起 UTI 的能力。使用 C3H/HeN 小鼠作为模型，对感染组织的组织学和免疫荧光分析表明，解脲支原体在膀胱中诱导上皮细胞脱落，并引起以巨噬细胞和中性粒细胞浸润为特征的炎症反应，在膀胱和肾脏中都有浸润。炎症反应与膀胱和肾脏中促炎细胞因子和趋化因子的产生增加相关。最后，我们观察到假定的解脲支原体毒力因子 Ssp 和 SdrI 对于在小鼠泌尿道中的持续存在很重要，但对于初始定植则不重要。因此，我们描述了参与解脲支原体 UTI 进展的宿主和细菌因素，并描述了一个用于研究这种革兰阳性尿路病原体发病机制的有用模型系统。
