Sexual transmission of urogenital bacteria: whole metagenome sequencing evidence from a sexual network study.

Sexual transmission of the urogenital microbiota may contribute to adverse sexual and reproductive health outcomes. The extent of sexual transmission of the urogenital microbiota is unclear as prior studies largely investigated specific pathogens. We used epidemiologic data and whole metagenome sequencing to characterize urogenital microbiota strain concordance between participants of a sexual network study. Individuals who screened positive for genital Chlamydia trachomatis were enrolled and referred their sexual contacts from the prior 60-180 days. Snowball recruitment of sexual contacts continued for up to four waves. Vaginal swabs and penile urethral swabs were collected for whole metagenome sequencing. We evaluated bacterial strain concordance using inStrain and network analysis. We defined concordance as ≥99.99% average nucleotide identity over ≥50% shared coverage; we defined putative sexual transmission as concordance between sexual contacts with <5 single-nucleotide polymorphisms per megabase. Of 138 participants, 74 (54%) were female; 120 (87%) had genital chlamydia; and 43 (31%) were recruited contacts. We identified 115 strain-concordance events among 54 participants representing 25 bacterial species. Seven events (6%) were between sexual contacts including putative heterosexual transmission of Fannyhessea vaginae, Gardnerella leopoldii, Prevotella amnii, Sneathia sanguinegens, and Sneathia vaginalis (one strain each), and putative sexual transmission of Lactobacillus iners between female contacts. Most concordance events (108, 94%) were between non-contacts, including eight female participants connected through 18 Lactobacillus crispatus and 3 Lactobacillus jensenii concordant strains, and 14 female and 2 male participants densely interconnected through 52 Gardnerella swidsinskii concordance events.IMPORTANCEEpidemiologic evidence consistently indicates bacterial vaginosis (BV) is sexually associated and may be sexually transmitted, though sexual transmission remains subject to debate. This study is not capable of demonstrating BV sexual transmission; however, we do provide strain-level metagenomic evidence that strongly supports heterosexual transmission of BV-associated species. These findings strengthen the evidence base that supports ongoing investigations of concurrent male partner treatment for reducing BV recurrence. Our data suggest that measuring the impact of male partner treatment on F. vaginae, G. leopoldii, P. amnii, S. sanguinegens, and S. vaginalis may provide insight into why a regimen does or does not perform well. We also observed a high degree of strain concordance between non-sexual-contact female participants. We posit that this may reflect limited dispersal capacity of vaginal bacteria coupled with individuals' comembership in regional transmission networks where transmission may occur between parent and child at birth, cohabiting individuals, or sexual contacts.

Chlamydia in adolescent/adult reproductive management trial study (CHARM): Clinical core protocol.

INTRODUCTION: Chlamydia trachomatis (CT) is a common sexually transmitted pathogen with significant reproductive health implications. Data are mounting that the bacterial communities that reside within the vagina, collectively termed the vaginal microbiota, aid in defense against sexually transmitted infections. Disruptions in the vaginal microbiota, such as during episodes of bacterial vaginosis, may increase susceptibility to infection. Herein, we describe the clinical core protocol for a NIH NIAID Cooperative Research Center titled Eco-Pathogenomic of Chlamydial Reproductive Tract Infection. The primary goals of the project are to describe the interrelationships between the urogenital microenvironment, the properties of the pathogen and immunologic responses of the host in men and women, and their association with clinical outcomes of CT infection in women. METHODS: Men and women with confirmed genital CT infections were recruited to a number of study protocols, including cross-sectional and longitudinal sub-studies. Participants completed a demographic and sexual health questionnaire and underwent a physical exam at baseline. In the longitudinal study arms, biologic samples were collected daily, weekly, and monthly to determine the relationships between the vaginal microbiota, prevalent CT infection, re-infection and treatment. DISCUSSION: The biological samples and the demographic and history information collected throughout this study will be used for various analyses evaluating genomics, metabolomics and host immune responses in the context of CT infection.