Ubiquitous gram-positive bacteria in the male urogenital tract are disease causing agents in chronic pelvic pain
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.
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