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Infection and Immunity, December 2009, p. 5245-5251, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00670-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

OmpA of Uropathogenic Escherichia coli Promotes Postinvasion Pathogenesis of Cystitis{triangledown}

Tracy F. Nicholson,1 Kristin M. Watts,1 and David A. Hunstad1,2*

Departments of Pediatrics,1 Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 631102

Received 11 June 2009/ Accepted 15 September 2009

Type 1 pilus directs bladder epithelial binding and invasion by uropathogenic Escherichia coli (UPEC) in the initial stage of cystitis, but the bacterial determinants of postinvasion events in the pathogenesis of cystitis are largely undetermined. We show here that the UPEC outer membrane protein A (OmpA), a monomeric, major, integral protein component of the bacterial outer membrane, functions as a critical determinant of intracellular virulence for UPEC, promoting persistent infection within bladder epithelium. Using a murine urinary tract infection (UTI) model, we demonstrate that whereas deletion of the UPEC ompA gene did not disrupt initial epithelial binding and invasion by UPEC, it did preclude completion of the intracellular bacterial community (IBC) pathway, accompanied by diminishing bacterial loads in the bladder. This defect in epithelial persistence of the ompA mutant was enhanced in competitive infections with wild-type UPEC. Microscopic examinations revealed that the ompA mutant formed significantly fewer IBCs, and those that were initiated were unable to progress past the early stages of maturation. These defects could be corrected by complementation of ompA. In addition, expression of ompA during wild-type UTI was sharply increased at time points correlated with IBC development and the arrival of host immune effector cells. Our findings establish OmpA as a key UPEC virulence factor that functions after epithelial invasion to facilitate IBC maturation and chronic bacterial persistence.

* Corresponding author. Mailing address: Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8208, St. Louis, MO 63110. Phone: (314) 286-2710. Fax: (314) 286-2895. E-mail: dhunstad{at}wustl.edu

{triangledown} Published ahead of print on 21 September 2009.

Editor: V. J. DiRita

Infection and Immunity, December 2009, p. 5245-5251, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00670-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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