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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