Sexual transmission of urogenital bacteria: whole metagenome sequencing evidence from a sexual network study
Authors: Carter Kayla A. , France Michael T. , Rutt Lindsay , Bilski Lisa , Martinez-Greiwe Sebastian , Regan Mary , Brotman Rebecca M. , Ravel Jacques 
Published: February 2024

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.

IMPORTANCE

Epidemiologic 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.