title: A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta.
abstract: Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury.
authors.affiliation: Department of Pediatric Infectious Diseases and 2 Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Christopher
authors.initials: C
authors.lastname: Whidbey
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Harrell
authors.forename: Kellie
authors.initials: K
authors.lastname: Burnside
authors.forename: Lisa
authors.initials: L
authors.lastname: Ngo
authors.forename: Alexis K
authors.initials: AK
authors.lastname: Becraft
authors.forename: Lakshminarayan M
authors.initials: LM
authors.lastname: Iyer
authors.forename: L
authors.initials: L
authors.lastname: Aravind
authors.forename: Jane
authors.initials: J
authors.lastname: Hitti
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Adams Waldorf
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajagopal
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism / Q000382:microbiology; D019286:Endopeptidase K / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000382:microbiology; D006017:Glycolipids / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000378:metabolism / Q000382:microbiology; D009952:Ornithine / Q000378:metabolism; D010860:Pigments, Biological / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism / Q000382:microbiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000378:metabolism / Q000382:microbiology*; D013290:Streptococcal Infections / Q000378:metabolism / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000378:metabolism*
chemical_list: D006017:Glycolipids; D006460:Hemolysin Proteins; D016328:NF-kappa B; D010860:Pigments, Biological; C418382:rhamnolipid; D009952:Ornithine; D019286:Endopeptidase K