Enterococcal Biofilm Formation and Virulence in an Optimized Murine Model of Foreign Body-Associated Urinary Tract Infections
Enterococcal Biofilm Formation and Virulence in an Optimized Murine Model of Foreign Body-Associated Urinary Tract Infections
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DOI：
10.1128/iai.00711-10
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Hultgren, Scott J.
中科院分区：
文献类型：
--
作者：
Guiton, Pascale S.;Hung, Chia S.;Hultgren, Scott J.
导管相关性尿路感染（CAUTI）构成了医院内尿路感染的大多数，并构成了重大的临床挑战。肠球菌属是肠炎的主要病原体之一。然而，很少有人知道肠球菌介导的尿路感染的病理生理学。我们优化了异物相关UTI的小鼠模型，以模拟患者留置导管的条件。在该模型中，异物的存在引起了主要的组织学变化，并诱导了膀胱中几种促炎细胞因子的表达。此外，与幼稚小鼠相比，用粪肠球菌感染导管植入小鼠诱导膀胱中白细胞介素1 β（IL-1 β）和巨噬细胞炎性蛋白1 α（MIP-1 α）的特异性表达。这些反应导致了一个有利的生态位的发展持久E。粪便感染的小鼠膀胱和肾脏。此外，体内导管植入物上的生物膜形成与持续感染相关。然而，肠球菌自溶因子GelE和Atn（也称为GREA）在体外生物膜形成中是重要的，在体内是不稳定的。相比之下，管家分选酶A（SrtA）对于Patients中的生物膜形成和毒力至关重要。总的来说，这种小鼠模型代表了对大肠杆菌感染的理解的一个重要进展，并强调了在大肠杆菌感染期间导尿的重要性。粪尿致病该模型也是鉴定毒力决定因子的有价值的工具，这些毒力决定因子可作为治疗肠球菌感染的潜在抗菌靶标。
Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial UTIs and pose significant clinical challenges. Enterococcal species are among the predominant causative agents of CAUTIs. However, very little is known about the pathophysiology of Enterococcus-mediated UTIs. We optimized a murine model of foreign body-associated UTI in order to mimic conditions of indwelling catheters in patients. In this model, the presence of a foreign body elicits major histological changes and induces the expression of several proinflammatory cytokines in the bladder. In addition, in contrast to naive mice, infection of catheter-implanted mice with Enterococcus faecalis induced the specific expression of interleukin 1 beta (IL-1 beta) and macrophage inflammatory protein 1 alpha (MIP-1 alpha) in the bladder. These responses resulted in a favorable niche for the development of persistent E. faecalis infections in the murine bladders and kidneys. Furthermore, biofilm formation on the catheter implant in vivo correlated with persistent infections. However, the enterococcal autolytic factors GelE and Atn (also known as AtlA), which are important in biofilm formation in vitro, are dispensable in vivo. In contrast, the housekeeping sortase A (SrtA) is critical for biofilm formation and virulence in CAUTIs. Overall, this murine model represents a significant advance in the understanding of CAUTIs and underscores the importance of urinary catheterization during E. faecalis uropathogenesis. This model is also a valuable tool for the identification of virulence determinants that can serve as potential antimicrobial targets for the treatment of enterococcal infections.