Group B Streptococcus β-hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo.
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.
Department of Pediatrics, Columbia University, New York, New York.
Tara M
TM
Randis
Department of Obstetrics and Gynecology, Weill-Cornell Medical Center, New York, New York.
Shari E
SE
Gelber
Department of Pediatrics, Columbia University, New York, New York.
Thomas A
TA
Hooven
Department of Pathology and Cell Biology, Columbia University, New York, New York.
Rosanna G
RG
Abellar
Department of Pediatrics, Columbia University, New York, New York.
Leor H
LH
Akabas
Department of Pediatrics, Columbia University, New York, New York.
Emma L
EL
Lewis
Department of Pediatrics, Columbia University, New York, New York.
Lindsay B
LB
Walker
Department of Pediatrics, Columbia University, New York, New York.
Leah M
LM
Byland
Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California.
Victor
V
Nizet
Department of Pediatrics, Columbia University, New York, New York.
Adam J
AJ
Ratner
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005313:Fetal Death / Q000139:chemically induced* / Q000209:etiology*; D006460:Hemolysin Proteins / Q000378:metabolism*; D006651:Histocytochemistry; D006801:Humans; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced* / Q000209:etiology*; D013290:Streptococcal Infections / Q000150:complications / Q000473:pathology*; D013292:Streptococcus agalactiae / Q000502:physiology*
D006460:Hemolysin Proteins
Streptococcus agalactiae; chorioamnionitis; perinatal infection; toxin