Genotoxicity and immunogenicity of the uropathogenic specific protein (USP) in the gut

PI: Baerga-Ortiz, Abel Title: Genotoxicity and immunogenicity of the uropathogenic specific protein (usp) in the gut Project Summary The uropathogenic specific protein (USP) is a multi-domain protein with nuclease activity harbored by some uropathogenic strains of Escherichia coli. The protein has been shown to cause damage to cultured endothelial cells. Although USP is primarily associated with urinary tract, the USP gene has been found in a large percentage of fecal samples screened across populations in Japan, USA and Puerto Rico. The presence of USP in fecal samples raises the question of 1) whether USP is toxic to the gastrointestinal tract and 2) whether this toxicity is a risk factor for intestinal disorders. This proposal is an effort to understand the gut-specific activity/toxicity of purified USP. Our group has already expressed and purified a USP protein with high nuclease activity. This R16 proposal details work that will be performed entirely by students, in which purified USP will be used to: 1) Investigate toxicity of USP against cultured patient-derived intestinal organoids, 2) Delineate possible mechanisms of USP entry into cultured patient-derived intestinal organoids, and 3) Explore whether the presence of USP in fecal samples is correlated with an anti-USP antibody response. All of the proposed experiments will help to ascertain a possible gut-specific activity of USP, which may impact disease risk.