Uropathogenic escherichia coli P and type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction

Keira Melican, Ruben M. Sandoval, Abdul Kader, Lina Josefsson, George A. Tanner, Bruce Molitoris, Agneta Richter-Dahlfors

Research output: Contribution to journalArticle

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Abstract

The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here we used multiphoton microscopy-based live animal imaging, combined with advanced surgical procedures, to investigate the role of uropathogenic Escherichia coli (UPEC) attachment organelles P and Type 1 fimbriae in renal bacterial infection. A GFP+ expressing variant of UPEC strain CFT073 and genetically well-defined isogenic mutants were microinfused into rat glomerulus or proximal tubules. Within 2 h bacteria colonized along the flat squamous epithelium of the Bowman's capsule despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow in the proximal tubule, the P and Type 1 fimbriae appeared to act in synergy to promote colonization. P fimbriae enhanced early colonization of the tubular epithelium, while Type 1 fimbriae mediated colonization of the center of the tubule via a mechanism believed to involve inter-bacterial binding and biofilm formation. The heterogeneous bacterial community within the tubule subsequently affected renal filtration leading to total obstruction of the nephron within 8 h. Our 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 center, or periphery, of a tubule lumen. Furthermore, our data show how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis.

Original languageEnglish
Article numbere1001298
JournalPLoS Pathogens
Volume7
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Uropathogenic Escherichia coli
Nephrons
Bacterial Infections
Epithelium
Bowman Capsule
Physiological Phenomena
Kidney
Pyelonephritis
Biofilms
Organelles
Microscopy
Bacteria
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Uropathogenic escherichia coli P and type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. / Melican, Keira; Sandoval, Ruben M.; Kader, Abdul; Josefsson, Lina; Tanner, George A.; Molitoris, Bruce; Richter-Dahlfors, Agneta.

In: PLoS Pathogens, Vol. 7, No. 2, e1001298, 02.2011.

Research output: Contribution to journalArticle

Melican, Keira ; Sandoval, Ruben M. ; Kader, Abdul ; Josefsson, Lina ; Tanner, George A. ; Molitoris, Bruce ; Richter-Dahlfors, Agneta. / Uropathogenic escherichia coli P and type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. In: PLoS Pathogens. 2011 ; Vol. 7, No. 2.
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