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Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2017-09-25 00:00:00 , DOI: 10.1073/pnas.1707572114
Jennifer N. Walker 1, 2 , Ana L. Flores-Mireles 1, 2 , Chloe L. Pinkner 1, 2 , Henry L. Schreiber 1, 2 , Matthew S. Joens 3 , Alyssa M. Park 4 , Aaron M. Potretzke 4 , Tyler M. Bauman 4 , Jerome S. Pinkner 1, 2 , James A. J. Fitzpatrick 3 , Alana Desai 4 , Michael G. Caparon 1, 2 , Scott J. Hultgren 1, 2
Affiliation  

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual’s susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus. Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA–Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host’s robust immune response.

中文翻译:

导尿改变膀胱生态,增强金黄色葡萄球菌感染尿路

耐甲氧西林金黄色葡萄球菌(MRSA)是导管相关性尿路感染(CAUTI)的新兴原因,其经常发展为更严重的侵袭性感染。我们调整了CAUTI的小鼠模型,以研究导管插入术如何增加个体对MRSA UTI的敏感性。该分析表明,MRSA需要导管插入术才能在膀胱中实现高水平的持续感染。如前所述,导管放置引起炎症反应,导致宿主蛋白纤维蛋白原(Fg)释放,从而覆盖了膀胱和植入物。感染后,我们显示MRSA以与沉积Fg共定位的模式附着于尿道上皮并植入。此外,MRSA加剧了宿主的炎症反应,刺激了Fg在尿道中的额外释放和积累,这促进了MRSA的定殖。与该模型一致,分析了患有以下疾病的患者的导管金黄色葡萄球菌阳性培养物显示,Fg与金黄色葡萄球菌共定位在导管上。在其他疾病模型中,聚集因子A和B(ClfA和ClfB)已显示出与MRSA-Fg相互作用的作用。我们发现,在突变体clfA有比突变显著更大的纤维蛋白原结合缺陷CLFB在体外试验中的几个。奇怪的是,只有CLFB -应变的CAUTI模型显著减弱。总之,这些数据表明导管插入术通过诱导Fg的释放来改变尿道环境,从而促进MRSA CAUTI发病机理,尽管宿主具有强大的免疫反应,病原体仍会增强其在尿道中的持久性。
更新日期:2017-09-26
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