Morbidity and mortality of human newborns are significant public health concerns. Group B Streptococci (GBS) are a significant cause of preterm births, stillbirths and early onset sepsis in human newborns. Although GBS normally reside as commensals in the lower genital tract (LGT) of healthy women, the events that promote transmission of GBS from the LGT to the fetus are unknown. Using human placenta and a guinea pig model of intrauterine infection, the objective of this proposal is to define environmental signals that activate virulence gene expression for ascending GBS infection and fetal injury.

Public Health Relevance

Understanding environmental signals that regulate virulence gene expression and promote bacterial penetration of human placenta leading to fetal injury will be beneficial in therapeutic strategies against preterm birth, stillbirth and early onset neonatal infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-IDM-B (80))
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GU, Xin-Xing
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Seattle Children's Hospital
United States
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Gendrin, Claire; Merillat, Sean; Vornhagen, Jay et al. (2018) Diminished Capsule Exacerbates Virulence, Blood-Brain Barrier Penetration, Intracellular Persistence, and Antibiotic Evasion of Hyperhemolytic Group B Streptococci. J Infect Dis 217:1128-1138
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Vornhagen, Jay; Armistead, Blair; Santana-Ufret, VerĂ³nica et al. (2018) Group B streptococcus exploits vaginal epithelial exfoliation for ascending infection. J Clin Invest 128:1985-1999
Gendrin, Claire; Shubin, Nicholas J; Boldenow, Erica et al. (2018) Mast cell chymase decreases the severity of group B Streptococcus infections. J Allergy Clin Immunol 142:120-129.e6
Harrell, Maria I; Burnside, Kellie; Whidbey, Christopher et al. (2017) Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection. J Infect Dis Med 2:
Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica et al. (2016) Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth. MBio 7:
Boldenow, Erica; Gendrin, Claire; Ngo, Lisa et al. (2016) Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor. Sci Immunol 1:
Gendrin, Claire; Vornhagen, Jay; Ngo, Lisa et al. (2015) Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection. Sci Adv 1:e1400225
Whidbey, Christopher; Vornhagen, Jay; Gendrin, Claire et al. (2015) A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury. EMBO Mol Med 7:488-505

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