Group B Streptococcus β-hemolysin/cytolysin Breaches Maternal-fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2014 Jan 30

PMID 24474814

Citations 75

Authors

Tara M Randis

Shari E Gelber

Thomas A Hooven

Rosanna G Abellar

Leor H Akabas

Emma L Lewis

Lindsay B Walker

Leah M Byland

Victor Nizet

Adam J Ratner

Affiliations

Soon will be listed here.

Abstract

Background: Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited.

Methods: We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection.

Results: Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver.

Conclusions: Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis.

Citing Articles

Characterization of the Cellular Immune Response to Group B Streptococcal Vaginal Colonization.

Spencer B, Nguyen D, Marroquin S, Gapin L, OBrien R, Doran K bioRxiv. 2025; .

PMID: 39975125 PMC: 11838357. DOI: 10.1101/2025.01.29.635275.

Virulence and pathogenicity of group B : Virulence factors and their roles in perinatal infection.

Megli C, Carlin S, Giacobe E, Hillebrand G, Hooven T Virulence. 2025; 16(1):2451173.

PMID: 39844743 PMC: 11758947. DOI: 10.1080/21505594.2025.2451173.

A CRISPRi Library Screen in Group B Identifies Surface Immunogenic Protein (Sip) as a Mediator of Multiple Host Interactions.

Firestone K, Gopalakrishna K, Rogers L, Peters A, Gaddy J, Nichols C bioRxiv. 2024; .

PMID: 39677656 PMC: 11643019. DOI: 10.1101/2024.12.06.627252.

Group B streptococcal infections in pregnancy and early life.

Manuel G, Twentyman J, Noble K, Eastman A, Aronoff D, Seepersaud R Clin Microbiol Rev. 2024; 38(1):e0015422.

PMID: 39584819 PMC: 11905376. DOI: 10.1128/cmr.00154-22.

The impact of butyrate on group B -induced intestinal barrier disruption.

Dominguez K, Pearah A, Lindon A, Worthington L, Carter R, John-Lewis Edwards N Infect Immun. 2024; 92(10):e0020024.

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