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Uropathogenic Escherichia coli P and Type 1 Fimbriae Act in Synergy in a Living Host to Facilitate Renal Colonization Leading to Nephron Obstruction Melican K, Sandoval RM, Kader A, Josefsson L, Tanner GA, et al. PLoS Pathogens, February 2011|Vol. 7|Issue 2|e1001298 Presenter : Feng-Ru Hsieh Commentator : Dr.Ching-Hao Teng Date/Time : 2010/1/5 16:10 -17:00 Location : Room 601,Med College Building Background: Uropathogenic E. coli (UPEC), the major cause of urinary tract infections (UTI), have evolved mechanisms to overcome numerous physiological challenges in infection. For successful colonization, bacterial attachments to the uroepithelium by Type 1 and P fimbriae have been studied. Lack of mono-mannose rich uroplakin on renal epithelia has previously implied that Type 1 fimbirae may play a minor role during kidney infection. However, the P fimbriae have been shown to be over-represented in clinical E. coli isolates from petients with pyelonephritis. Recently, the live animal multiphoton microscopy (MPM) has been utilized to visualize tissue dynamics during renal bacterial infections. The real-time visualization studies of the infection process can be performed under the influence of all physiological factors. The spatial-temporal control of the infection is achieved by slowly injecting bacteria into superficial proximal tubules of surgically exposed kidneys in anesthetized rats. Objective: To investigate the roles of P and Type 1 fimbriae in UPEC renal colonization under dynamic in vivo conditions. Results: In this study, a GFP+ expressing variant of UPEC strain CFT073 and isogenic mutants were injected into rat glomerulus or proximal tubules. According to the live animal multiphoton microscopy (MPM), the bacteria colonized along the epithelium of the Bowman’s capsule within 2 h after infection, despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow, P and Type 1 fimbriae worked together to promote successful colonization. P fimbriae mediated binding between the bacteria and the epithelial cells of the tubule lumen, enhancing early colonization. Type 1 fimbriae appeared to play a role in inter-bacterial binding and biofilm formation, mediating colonization of the center of the tubule. The heterogeneous bacterial community, which filled the tubule, was shown to effect nephron filtration and subsequently resulted in a total loss of filtrate flow within 8 h. Conclusion: The results reveal the importance of physiological factors such as filtration in determining bacterial colonization patterns and demonstrate that the spatial resolution of an infectious niche can be as small as the tubule lumen. Furthermore, the data indicate how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis. Finally, the dynamic imaging within a live animal model has great potential to define new physiologically/clinically relevant outcomes of the complex microbe-host interplay. References: Mansson LE, Melican K, Boekel J, Sandoval RM, Hautefort I, et al. (2007) Real-time studies of the progression of bacterial infections and immediate tissue responses in live animals. Cell Microbiol 9: 413–424