OmpA of uropathogenic Escherichia coli promotes postinvasion pathogenesis of cystitis.
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.
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Tracy F
TF
Nicholson
Kristin M
KM
Watts
David A
DA
Hunstad
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D015169:Colony Count, Microbial; D003556:Cystitis / Q000382:microbiology*; D005260:Female; D017353:Gene Deletion; D005816:Genetic Complementation Test; D051379:Mice; D008809:Mice, Inbred C3H; D001743:Urinary Bladder / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
D001425:Bacterial Outer Membrane Proteins; D037521:Virulence Factors; C078167:OMPA outer membrane proteins