Morbidity and mortality of human newborns are significant public health concerns. Predominant risk factors for neonatal morbidity and mortality are invasive bacterial infections and the ensuing severe inflammatory response, which mainly begin in utero. Group B Streptococci (GBS) are a significant cause of preterm births, stillbirths and early onset neonatal disease. Factors that facilitate ascending GBS infection from the lower genital tract to the fetus are not understood. Our studies indicate that upregulation of virulence factors facilitate GBS invasion of placental membranes in vitro. Using human placental membranes and a nonhuman primate model, the objective of this proposal is to mechanistically define how virulence factors enable ascending in utero GBS infection and subsequent fetal lung and brain injury.

Public Health Relevance

Understanding mechanisms of ascending GBS infection and fetal injury will be beneficial for development of therapeutic strategies against in utero infectios that lead to fetal injury, preterm births, and stillbirths.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI100989-03
Application #
8688141
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
GU, Xin-Xing
Project Start
2012-07-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98121
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Vornhagen, Jay; Quach, Phoenicia; Santana-Ufret, VerĂ³nica et al. (2018) Human Cervical Mucus Plugs Exhibit Insufficiencies in Antimicrobial Activity Towards Group B Streptococcus. J Infect Dis 217:1626-1636
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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