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.
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Proceedings of the National Academy of Sciences of the United States of America. 2017 Sep 25 [Epub]
Jennifer N Walker, Ana L Flores-Mireles, Chloe L Pinkner, Henry L Schreiber, Matthew S Joens, Alyssa M Park, Aaron M Potretzke, Tyler M Bauman, Jerome S Pinkner, James A J Fitzpatrick, Alana Desai, Michael G Caparon, Scott J Hultgren
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110., Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO 63110., Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO 63110., Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110; .