Maturation of intracellular Escherichia coli communities requires SurA.
Escherichia coli is the most common cause of community-acquired urinary tract infection (UTI). During murine cystitis, uropathogenic E. coli (UPEC) utilizes type 1 pili to bind and invade superficial bladder epithelial cells. UPEC then replicates within to form intracellular bacterial communities (IBCs), a process whose genetic determinants are as yet undefined. In this study, we investigated the role of SurA in the UPEC pathogenic cascade. SurA is a periplasmic prolyl isomerase/chaperone that facilitates outer membrane protein biogenesis and pilus assembly in E. coli. Invasion into bladder epithelial cells was disproportionately reduced when surA was genetically disrupted in the UPEC strain UTI89, demonstrating that binding alone is not sufficient for invasion. In a murine cystitis model, UTI89 surA::kan was unable to persist in the urinary tract. Complementation of UTI89 surA::kan with a plasmid (pDH15) containing surA under the control of an arabinose-inducible promoter restored in vivo binding and invasion events. However, the absence of arabinose within the mouse bladder resulted in depletion of SurA after invasion of the bacteria into the superficial epithelial cells. Under these conditions, invasion by UTI89/pDH15 surA::kan was normal, but in contrast to UTI89, UTI89/pDH15 surA::kan formed intracellular collections that contained fewer bacteria, were loosely organized, and lacked the normal transition to a densely packed, coccoid morphology. Our data argue that SurA is required within bladder epithelial cells for UPEC to undergo the morphological changes that underlie IBC maturation and completion of the UTI pathogenic cascade.
Justice
Sheryl S
SS
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lauer
Scott R
SR
Hultgren
Scott J
SJ
Hunstad
David A
DA
D018830:Adhesins, Escherichia coli / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003556:Cystitis / Q000382:microbiology; D017753:Ecosystem; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000254:growth & development* / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D036781:Fimbriae Proteins / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D018613:Microscopy, Confocal; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000166:cytology / Q000382:microbiology; D014552:Urinary Tract Infections / Q000382:microbiology*; D014774:Virulence
D018830:Adhesins, Escherichia coli; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; C490900:SurA protein, E coli; D019696:Peptidylprolyl Isomerase