Human Urithritis Microbiome Project

Urethritis is an extremely common male urogenital syndrome which triggers hundreds of thousands of clinic visits per annum in the US alone. In addition to acute symptoms, urethritis augments HIV shedding in semen, increases susceptibility to other sexually transmitted infections (STI) and can precipitate long lasting pathology. Urethritis is strongly associated with known STI including C. trachomatis and N. gonorrhea but 20-50% of all cases are idiopathic. Clinical observations indicate idiopathic urethritis is caused by unknown bacterial and or viral pathogens and is sometimes sexually transmitted. In contrast, large proportions of men infected with known STI, most frequently C. trachomatis, are asymptomatic. Identifying causes of idiopathic urethritis, and factors which dictate if STI elicit urethritis would alter existing paradigms for STI control in both sexes and clinical management of urethritis in men.

We plan to survey urine samples from men at high risk for STI using 16S rRNA and shotgun sequencing. Our preliminary results have determined that these men were frequently colonized with fastidious uncultivated bacteria. Many bacteria identified in male urine were previously identified as vaginal flora, and known but uncultivated female reproductive tract pathogens were common. We also observed that the urogenital microbiomes of healthy men, men with asymptomatic STI and men with urethritis differed markedly. Our data imply uncharacterized urogenital tract microorganisms elicit idiopathic urethritis and may modulate symptoms and or persistence of STI, such as C. trachomatis. Our specific aims are to:

  1. Identify etiological agents of idiopathic urethritis by comparing the microbiomes of men with idiopathic urethritis, urethritis caused by known STI and healthy men.
  2. Determine whether symptoms during C. trachomatis infection are associated with specific microbial communities.
  3. Sequence and annotate genomes of uncultivated urogenital tract pathogens and commensals.