Characterization of a Novel Murine Model of Staphylococcus saprophyticus Urinary Tract Infection Reveals Roles for Ssp and SdrI in Virulence
Characterization of a Novel Murine Model of Staphylococcus saprophyticus Urinary Tract Infection Reveals Roles for Ssp and SdrI in Virulence
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DOI：
10.1128/iai.01235-09
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发表时间：
2010-05-01
影响因子：
3.1
通讯作者：
Hultgren, Scott J.
中科院分区：
文献类型：
--
作者：
Kline, Kimberly A.;Ingersoll, Molly A.;Hultgren, Scott J.
金黄色葡萄球菌是一种专性人类病原体，是年轻健康女性尿路感染（UTI）最常见的革兰氏阳性病原体。尽管S.然而，关于它如何引起尿路疾病或宿主如何对感染作出反应，人们知之甚少。在此，我们建立了一个体内模型来研究宿主和细菌因素对S。红蜘蛛UTI.利用这个模型，我们证明了S.嗜铬链球菌优先感染C3 H/HeN鼠肾而不是膀胱，这是在多种临床分离株中观察到的特征。在C3 H/HeN小鼠中观察到细菌在肾脏中的持久性，但在C57 BL/6小鼠中未观察到，表明宿主因素强烈有助于S.引起尿路感染的原因。以C3 H/HeN小鼠为模型，感染组织的组织学和免疫荧光分析表明，S. sageticus诱导膀胱中的上皮细胞脱落和以膀胱和肾中的巨噬细胞和嗜中性粒细胞浸润为特征的炎症反应。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S。Ssp和SdrI是重要的持久性，但不是最初的殖民，在小鼠泌尿道。因此，我们确定了参与S. sachticus UTI，我们描述了一个有用的模型系统，用于研究参与这种革兰氏阳性尿路病原体的发病机制的因素。
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.