Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection
Jay Vornhagen, … , Elizabeth Nance, Lakshmi Rajagopal
Jay Vornhagen, … , Elizabeth Nance, Lakshmi Rajagopal
Published April 9, 2018
Citation Information: J Clin Invest. 2018;128(5):1985-1999. https://doi.org/10.1172/JCI97043.
View: Text | PDF
Research Article Infectious disease Reproductive biology Article has an altmetric score of 37

Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection

  • Text
  • PDF
Abstract

Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and β-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.

Authors

Jay Vornhagen, Blair Armistead, Verónica Santana-Ufret, Claire Gendrin, Sean Merillat, Michelle Coleman, Phoenicia Quach, Erica Boldenow, Varchita Alishetti, Christina Leonhard-Melief, Lisa Y. Ngo, Christopher Whidbey, Kelly S. Doran, Chad Curtis, Kristina M. Adams Waldorf, Elizabeth Nance, Lakshmi Rajagopal

×

Figure 1

GBS stimulates exfoliation and disrupts vaginal epithelial cell barrier function in vitro.

Options: View larger image (or click on image) Download as PowerPoint
GBS stimulates exfoliation and disrupts vaginal epithelial cell barrier ...
(A) hVECs were infected with WT GBS for 0, 16, or 24 hours and stained with 10% crystal violet for 30 minutes. Loosely adherent cells were removed by centrifugation, and crystal violet staining intensity was measured. Data were normalized to mock-infected controls (n = 3; **P < 0.005 and P = 0.08, by ANOVA followed by Sidak’s multiple comparisons test; data represent the mean ± SEM). (B) hVECs were infected with WT GBS for 24 hours and analyzed by scanning electron microscopy. Images show hVEC detachment 24 hours after infection with control PBS (mock) or WT GBS. Scale bars: 10 μm. (C) The barrier function of hVEC monolayers was monitored in real time using ECIS. Infection with WT GBS led to a disruption in barrier function as determined by the decrease in resistance of the infected monolayers compared with the uninfected control (n = 3; data represent the mean). (D) hVECs grown on Transwells were infected with WT GBS for 24 hours or treated with 0.1% Triton X-100, which was used as a positive control. After 24 hours, fluorescein dye was added to the apical compartment of the Transwell, and migration of the dye to the basal compartment was measured after 1 hour (n = 3; ****P < 0.00005, by ANOVA followed by Sidak’s multiple comparisons test; data represent the mean ± SEM). (E) hVECs grown on Transwells were either mock infected or infected with WT GBS for 24 hours. At 0, 16, and 24 hours after infection, the basal compartment of each well was sampled and stained with SYTO9 nucleic acid to enumerate bacteria (n = 3; **P < 0.005, by ANOVA followed by Sidak’s multiple comparisons test; data represent the mean ± SEM). RFU, relative fluorescence units.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 3 news outlets
Blogged by 1
Posted by 17 X users
On 2 Facebook pages
Highlighted by 1 platforms
118 readers on Mendeley
See more details