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 I 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 UT189, demonstrating that binding alone is not sufficient for invasion. In a murine cystitis model, UT189 surA::kan was unable to persist in the urinary tract. Complementation of UT189 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 UT189/pDHI5 surA::kan was normal, but in contrast to UT189, UT189/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.