Urinary Tract InfectionUPEC genomics/geneticsChaperone/Usher Pathway PiliEnterococcal pathogenesis/catheter-associated UTIBacterial amyloid (Curli) biogenesisBacterial Community Interactions (Biofilms and Microbiome)Drug and Vaccine Development

Enterococcal pathogenesis/catheter-associated UTI

Catheter-associated urinary tract infections (CAUTIs) are one of the most common nosocomial infections and if untreated can lead to serious complications including bacteremia and death. Enterococcus faecalis is a leading causative agent of CAUTI and prevention and treatment are hindered by its ability to adhere to and persist within the host and on hospital surfaces. Furthermore, E. faecalis is inherently resistance to many antimicrobials, and there is increasing prevalence of strains resistant to multiple antibiotics.

Colocalization between E.faecalis and fibrinogen

E. faecalis co-localized with fibrinogen on implanted mouse bladder during CAUTI.
Nuclei in blue, mouse uroplakin III in red, fibrinogen in green and E. faecalis in purple.

E. faecalis can form biofilms on indwelling medical devices, such as urinary catheters, and grow despite a robust inflammatory response. The molecular details of how E. faecalis adheres, grows in the bladder, forms biofilms and the importance of biofilm in persistence in CAUTI are not well understood. We have delineated aspects of the ability of E. faecalis to elaborate a sortase assembled pilus, the endocarditis- and biofilm-associated pilus (Ebp), as well as aspects of localized secretion of proteins in E. faecalis.

We have developed a mouse model of CAUTI, which mimics many of the features of clinical disease. Using this model we have elucidated aspects of E. faecalis CAUTI pathogenesis and demonstrated that EbpA, the adhesin of Ebp, which contains a metal ion-dependent adhesion site (MIDAS), is required for E. faecalis colonization in a catheter-implanted bladder. Further characterization of EbpA binding, along with determination of the pathogenic mechanisms by which E. faecalis causes disease will aid in the identification of novel therapeutic targets for E. faecalis CAUTI.
Collaborators: Mike Caparon.