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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.
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Research Article Infectious disease Reproductive biology

Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection

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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

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Figure 3

GBS induces EMT.

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GBS induces EMT.
Flow cytometric analysis of surface E-cadherin (A) or N...
Flow cytometric analysis of surface E-cadherin (A) or N-cadherin (B) expression on GBS-infected hVECs compared with the mock (PBS) control (n = 3; **P < 0.005 and ***P < 0.0005, by 2-sided, unpaired t test; data represent the mean ± SEM). (C) Quantitative reverse transcription PCR analysis of EMT markers in GBS-infected hVECs compared with mock-treated controls (n = 3; **P < 0.005 and ****P < 0.00005, by 1-way ANOVA followed by Sidak’s multiple comparisons test; data represent the mean ± SEM). (D) E-cadherin immunostaining in murine vaginal tracts 24 and 96 hours after vaginal inoculation with PBS or WT GBS, respectively. Images are from 1 of 3 experiments. Scale bars: 100 μm. (E) Flow cytometric analysis of surface E-cadherin on CD326+ mVECs 96 hours after vaginal inoculation with WT GBS or control PBS (n = 6 mice/group; *P < 0.05, by 2-sided, unpaired t test; data represent the mean).
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