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Escherichia coli from Urine of Female Patients with Urinary Tract Infections Is Competent for Intracellular Bacterial Community Formation

Corinne K. Garofalo,¹ Thomas M. Hooton,^2, Steven M. Martin,^1, Walter E. Stamm,² Joseph J. Palermo,¹ Jeffrey I. Gordon,³ and Scott J. Hultgren^1*

Department of Molecular Microbiology and Microbial Pathogenesis, Washington University School of Medicine, St. Louis, Missouri 63110,¹ Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195,² Center for Genome Sciences, Washington University School of Medicine, St. Louis, Missouri 63108³

Received 13 July 2006/ Returned for modification 12 September 2006/ Accepted 13 October 2006

Nearly 50% of women experience at least one urinary tract infection (UTI) in their lifetime. Studies with mice have revealed that uropathogenic Escherichia coli (UPEC) isolates 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, 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 coinoculated with an isolate that was capable of generating IBCs. The mixed infections dramatically altered the behavior of the coinfecting 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 isolates differ genetically in their virulence factors, the majority of UPEC isolates from different types of UTI proceed through the IBC pathway, confirming the generality of IBCs in UTI pathogenesis in mice.

Published ahead of print on 30 October 2006.

Editor: A. D. O'Brien

Present address: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136.

Present address: Sequoia Sciences, 1912 Innerbelt Business Center Dr., St. Louis, MO 63114.

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