Gardnerella vaginalis promotes group B Streptococcus vaginal colonization, enabling ascending uteroplacental infection in pregnant mice

Nicole M. Gilbert, Lynne R. Foster, Bin Cao, Yin Yin, Indira U. Mysorekar, Amanda L. Lewis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a “dysbiotic” polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse models of group B Streptococcus and Gardnerella vaginalis colonization have been reported but, to the best of our knowledge, the two have not been studied together. The overarching idea driving this study is that certain members of the dysbiotic vaginal microbiota, such as Gardnerella vaginalis, may directly contribute to the increased rate of group B Streptococcus vaginal colonization observed in women with vaginal dysbiosis. Objective: We used a mouse model to test the hypothesis that vaginal exposure to Gardnerella vaginalis may facilitate colonization and/or invasive infection of the upper reproductive tract by group B Streptococcus during pregnancy. Study Design: Timed-pregnant mice were generated using an allogeneic mating strategy with BALB/c males and C57Bl/6 females. Dams were vaginally inoculated at gestational day 14 with group B Streptococcus alone (using a 10-fold lower dose than previously reported models) or coinoculated with group B Streptococcus and Gardnerella vaginalis. Bacterial titers were enumerated in vaginal, uterine horn, and placental tissues at gestational day 17. The presence (Fisher exact tests) and levels (Mann-Whitney U tests) of bacterial titers were compared between mono- and coinoculated dams in each compartment. Relative risks were calculated for outcomes that occurred in both groups. Tissue samples were also examined for evidence of pathophysiology. Results: Inoculation of pregnant mice with 107 group B Streptococcus alone did not result in vaginal colonization or ascending infection. In contrast, coinoculation of group B Streptococcus with Gardnerella vaginalis in pregnant mice resulted in a 10-fold higher risk of group B Streptococcus vaginal colonization (relative risk, 10.31; 95% confidence interval, 2.710–59.04; P=.0006 [Fisher exact test]). Ascending group B Streptococcus infection of the uterus and placenta occurred in approximately 40% of coinoculated animals, whereas none of those receiving group B Streptococcus alone developed uterine or placental infections. Immunofluorescence microscopy revealed group B Streptococcus in both the maternal and fetal sides of the placenta. Histologic inflammation and increased proinflammatory cytokines were evident in the setting of group B Streptococcus placental infection. Interestingly, placentas from dams exposed to group B Streptococcus and Gardnerella vaginalis, but without recoverable vaginal or placental bacteria, displayed distinct histopathologic features and cytokine signatures. Conclusion: These data suggest that Gardnerella vaginalis vaginal exposure can promote group B Streptococcus vaginal colonization, resulting in a greater likelihood of invasive perinatal group B Streptococcus infections. These findings suggest that future clinical studies should examine whether the presence of Gardnerella vaginalis is a risk factor for group B Streptococcus vaginal colonization in women. Because Gardnerella vaginalis can also be present in women without bacterial vaginosis, these findings may be relevant both inside and outside of the context of vaginal dysbiosis.

Original languageEnglish
Pages (from-to)530.e1-530.e17
JournalAmerican journal of obstetrics and gynecology
Volume224
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • Gardnerella vaginalis
  • ascending infection
  • bacterial vaginosis
  • group B Streptococcus
  • health disparities
  • microbiota
  • placenta
  • uterus
  • vagina
  • vaginal microbiome

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