Group B Streptococcus β-hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo

J Infect Dis. 2014 Jul 15;210(2):265-73. doi: 10.1093/infdis/jiu067. Epub 2014 Jan 28.


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.

Keywords: Streptococcus agalactiae; chorioamnionitis; perinatal infection; toxin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fetal Death / chemically induced*
  • Fetal Death / etiology*
  • Hemolysin Proteins / metabolism*
  • Histocytochemistry
  • Humans
  • Liver / microbiology
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Premature Birth / chemically induced*
  • Premature Birth / etiology*
  • Streptococcal Infections / complications
  • Streptococcal Infections / pathology*
  • Streptococcus agalactiae / physiology*


  • Hemolysin Proteins