Praveen Thumbikat1, Stephen F. Murphy1, Jonathan F. Anker1, Daniel J. Mazur1, Anthony J. Schaeffer1, Christel Hall1

1Feinberg School of Medicine, Northwestern University, Chicago, IL 60611

Gram-positive bacteria are considered an ubiquitous but incidental finding in urine and prostatic secretion cultures from male patients with chronic pelvic pain syndrome (CPPS) However, we hypothesized that gram-positive traditional non-uropathogenic bacteria can play a direct role in CPPS pathogenesis. Staphylococcus epidermidis, Staphylococcus haemolyticus, and Enterococcus faecalis comprised 62% of prostate-localizing bacteria from CPPS patients. A subset of these induced high NFκB expression, contained pathogenic virulence factors, and were associated with increased clinical symptoms. Here we show that an immunogenic subset of the most common gram-positive prostate-localizing bacterial strains can directly cause pelvic tactile allodynia and voiding dysfunction. Intra-urethral infection of mice with immunogenic bacterial isolates from each strain, but not an S. epidermidis isolate from a healthy control, recapitulated symptoms seen in patients. Mechanistically, these pathogenic gram-positive bacteria induced unique prostate inflammation, involving T cells, NK cells, and cytokine production. We demonstrate for the first time that the prevalent, yet untreated traditional non-uropathogenic gram-positive bacteria can play a causative role in CPPS pathogenesis.