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Infect. Immun. doi:10.1128/IAI.01123-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

ESCHERICHIA COLI FROM URINE OF FEMALES SUFFERING FROM URINARY TRACT INFECTIONS ARE COMPETENT FOR IBC-FORMATION

Corinne K. Garofalo, Thomas M. Hooton, Steven M. Martin, Walter E. Stamm, Joseph J. Palermo, Jeffrey I. Gordon, and Scott J. Hultgren*

Department of Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, Missouri 63110; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195; Center for Genome Sciences, Washington University School Medicine, St. Louis, Missouri 63108

* To whom correspondence should be addressed. Email: hultgren{at}borcim.wustl.edu.


   Abstract

Nearly 50% of women experience at least one UTI in their lifetime. Studies in mice have revealed that uropathogenic E. coli (UPEC) invade superficial umbrella cells that line the bladder, allowing them to find a safe haven and subvert clearance by innate host responses. Rapid intracellular replication results in the formation of distinctive intracellular bacterial communities (IBCs). In this study, we evaluated whether UPEC strains, cultured from the urine of women and classified as causing acute cystitis, recurrent cystitis, asymptomatic bacteriuria (ASB), or pyelonephritis, could progress through the IBC cascade in a well-characterized mouse model of cystitis. Of 18 UPEC isolates collected from women, 15 formed IBCs. Variations in the size, number, and kinetics of IBC formation were observed with strains isolated from women with different clinical syndromes. Two of the three isolates that did not form IBCs when inoculated alone, were able to do so when co-inoculated with an isolate that was capable of generating IBCs. The mixed infections dramatically altered the behavior of the co-infecting bacteria relative to their behavior in a single infection. The study also showed that mice with five different genetic backgrounds can support IBC formation. Although UPEC differ genetically in their virulence factors, the majority of UPEC from different syndromes of UTI proceed through the IBC pathway confirming the universality of IBCs in UTI pathogenesis in mice.




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