Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection

• Published in: The Journal of clinical investigation Vol. 128; no. 5; pp. 1985 - 1999
• Main Authors: Vornhagen, Jay, Armistead, Blair, Santana-Ufret, Verónica, Gendrin, Claire, Merillat, Sean, Coleman, Michelle, Quach, Phoenicia, Boldenow, Erica, Alishetti, Varchita, Leonhard-Melief, Christina, Ngo, Lisa Y, Whidbey, Christopher, Doran, Kelly S, Curtis, Chad, Waldorf, Kristina M Adams, Nance, Elizabeth, Rajagopal, Lakshmi
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-05-2018
• Subjects: Animal models; Animals; anticancer drugs; Bacteria; Bacterial infections; Biomedical research; Cancer; Colonization; Complications and side effects; Defense mechanisms; Development and progression; Epithelial Cells - immunology; Epithelial Cells - microbiology; Epithelial Cells - pathology; Exfoliation; expression; Female; Health aspects; in-vivo; Infections; Infectious Medicine; Infektionsmedicin; Kinases; lipoteichoic acid; maternal colonization; mesenchymal; Mice; Mice, Knockout; neonatal disease; Obstetrics, Gynecology and Reproductive Medicine; Pregnancy; Pregnancy complications; Premature birth; preterm birth; Reproduktionsmedicin och gynekologi; Research & Experimental Medicine; Risk factors; Signal transduction; squamous-cell carcinoma; Stillbirth; Streptococcal infections; Streptococcal Infections - immunology; Streptococcal Infections - pathology; Streptococcus; Streptococcus agalactiae; Streptococcus agalactiae - immunology; Streptococcus infections; transition; uropathogenic escherichia-coli; Uterine diseases; Uterus; Vagina; Vagina - immunology; Vagina - microbiology; Vagina - pathology; Vaginosis, Bacterial - immunology; Vaginosis, Bacterial - microbiology; Vaginosis, Bacterial - pathology; Viral infections; β-Catenin; Infectious disease; Reproductive Biology; Bacterial infections
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI97043

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.