Gram Positive & Polymicrobial Interactions in Urinary Tract Infection

Urinary tract infection (UTI) is one of the most common bacterial infections in humans. Approximately 80% of community-acquired UTI and >50% of hospital-acquired UTI are caused by Gram negative uropathogenic Escherichia coli (UPEC). The remainder of UTI are cause by a consortium of uropathogens including Gram positive Staphylococcus saprophyticus, Group B Streptococcus (GBS), and Enterococci. In addition, catheter-associated UTI (CA-UTI) account for 40% of all nosocomial infections, and Enterococcus faecalis and Enterococcus faecium cause 15-30% of CA-UTI. UPEC UTI is associated with a robust acute inflammatory response that includes cytokine production, neutrophil recruitment, and exfoliation. In contrast, we have shown that the Gram positive uropathogens S. saprophyticus, GBS, and E. faecalis elicit a minimal response from the host. Remarkably, E. faecalis persist at titers of >10^7 CFU/ml in a biofilm state during CA-UTI and still evoke little to no host immune response. Using in vitro and in vivo infection models, we are examining mechanisms by which Gram positive uropathogens, such as E. faecalis, interact with the host to cause disease during monomicrobial, polymicrobial, and catheter-associated infections.