Urethritis is the most common male reproductive tract syndrome, yet up to 50% of cases have no known etiology. Recently, we found that Leptotrichia/Sneathia spp., newly described bacteria that are highly sensitive and specific for bacterial vaginosis (BV) in women, were significantly associated with idiopathic urethritis in men. Two other newly described bacteria (BV-associated bacterium [BVAB] 2, and BVAB3) were found more often in men with idiopathic urethritis than in control men, suggesting that all 3 of these bacteria may play a role in urethritis. Furthermore, men with idiopathic urethritis had urethral microbial communities that were distinct from those in healthy men, and relative abundance of Lactobacillis iners was consistently higher in men with urethritis, suggesting that changes in the urethral microbiota may also play a causal role in the development of urethritis. Given the relatively common nature of male urethritis, its propensity to recur, and the high proportion of unexplained cases, we propose a 2-tiered strategy to identify novel etiologies of this condition. In a species-specific approach, we will prospectively assess the relationship between 3 newly described bacteria (Leptotrichia/Sneathia spp., BVAB2, BVAB3) and the incidence, resolution and recurrence of urethritis using species-specific quantitative PCR. In a metagenomic approach, we will use broad range 16S rRNA gene PCR with pyrosequencing to describe the urethral bacterial biota in men over time and to assess whether changes in species composition of bacteria in microbial communities and/or relative abundance of specific bacteria (L. iners, among others) are associated with incidence, resolution and recurrence of urethritis. Finally, we hypothesize that these bacteria and bacterial communities are sexually transmitted and will assess the relationships between specific sexual exposures, acquisition of any of the 3 newly described bacteria and/or changes in microbial communities, and new onset of clinical signs and symptoms of urethritis. These studies will enhance the clinical management of male urethritis, and may lead to the development of new diagnostic tools, therapies and prevention strategies. Given the sexually transmitted nature of most genital tract bacteria, parallel benefits for clinical management of female reproductive tract disease may follow.

Public Health Relevance

The majority of male urethritis cases have no identified etiology. The proposed species-specific analyses will evaluate whether newly described bacteria in women with BV also play a role in male urethritis, leading to better guidance in the clinical management of NGU. Metagenomic analyses will provide novel information on the role of microbial communities and microbial diversity in male genital tract disease. Sexually transmitted organisms are often associated with male and female reproductive tract disease, and identification of novel pathogenic organisms and/or microbial communities may lead to new treatment and prevention strategies for both men and women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI110666-01
Application #
8672151
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
David, Hagit S
Project Start
2014-03-03
Project End
2019-02-28
Budget Start
2014-03-03
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$809,919
Indirect Cost
$173,755
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195