Interplay of heterosexual male-female partner microbiomes, Chlamydia trachomatis and transmission

About This Grant

SUMMARY Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted infections (STI) worldwide. About 128M Ct cases are estimated to occur annually according to the WHO and 1.6M in the US. The Western Pacific Region (WPR) has over 61M of these global infections with a prevalence of ~35-40% among adolescents and young adults under the age of 25 years. About 50% of men and 80% of women are asymptomatic. Syndromic management—the reliance on signs and symptoms of STIs to determine the need for antibiotics—is often practiced in this region but is imprecise, leading to unchecked transmission to partners. Complications from these infections include infertility, pre-term birth and proctitis in addition to an increased risk of HIV and other STIs. Studies of Ct STIs focus primarily on female urogenital infections and rectal infections among men who have sex with men (MSM) with few studies of urethral infections among men who have sex only with women (MSW). While the US Centers for Disease Control (CDC) recommends annual Ct screening for women under 25 years and those at high risk (e.g., multiple partners), screening for MSW is not recommended, This leaves a gap in our knowledge about MSW urethral Ct infections and transmission dynamics to and from female partners. Our unifying hypothesis is that Ct infection, transmission and disease pathogenesis are driven/perpetuated by the interaction of male urethral and female partner endocervical, vaginal and rectal microbiomes and host immune responses that are influenced by Ct infections. For the proposed research, we will study a large cohort of male- female partners with a high prevalence of Ct in the male urethra and female endocervix, vagina and rectum. The microbiomes of these sites will be characterized by metagenome shotgun sequencing (MSS), the host immune responses by quantitative protein assays, and the Ct genomic characteristics by whole genome sequencing (WGS) and the respective analyses. Resistomes (i.e., antibiotic resistance genes (ARGs) or mutations conferring resistance to antibiotics) that are part of the microbiome will also be interrogated. Given our unique samples and metadata on all partners in this cohort, we aim to: 1) Evaluate the association between male urethral microbiomes and presence or absence of Ct; 2) Correlate male urethral microbiomes and Ct strains with similar data from female partners; 3) Model how microbiomes, including the resistome, host immune responses and Ct strains predict transmission, infection risk and disease pathogenesis. This study will create the most extensive dataset on male urethral microbiomes, resistomes, and host immune responses to date, providing a valuable resource for the medical and scientific community. Further, given the growing number of Ct STIs in the US and worldwide, the proposed research provides a unique opportunity to study male-female partners and within-host transmission to identify microbiome/resistome//inflammatory profiles that may promote Ct transmission and infection and how these data can be translated into Ct prevention and control strategies. These strategies may include identifying sentinel sites for targeted Ct screening and developing beneficial microbial therapeutics for topical therapy.