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 #
3R01AI100989-03S1
Application #
8908546
Study Section
Special Emphasis Panel (ZAI1-BDP-M (M1))
Program Officer
GU, Xin-Xing
Project Start
2012-07-01
Project End
2017-06-30
Budget Start
2014-08-15
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
$78,195
Indirect Cost
$34,931
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
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Li, Junwei; Baird, Madison A; Davis, Michael A et al. (2017) Dramatic enhancement of the detection limits of bioassays via ultrafast deposition of polydopamine. Nat Biomed Eng 1:
Vornhagen, Jay; Adams Waldorf, Kristina M; Rajagopal, Lakshmi (2017) Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies. Trends Microbiol 25:919-931
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Gendrin, Claire; Vornhagen, Jay; Armistead, Blair et al. (2017) A non-hemolytic Group B Streptococcus strain exhibits hypervirulence. J Infect Dis :
Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica et al. (2016) Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth. MBio 7:
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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
Gendrin, Claire; Lembo, Annalisa; Whidbey, Christopher et al. (2015) The sensor histidine kinase RgfC affects group B streptococcal virulence factor expression independent of its response regulator RgfA. Infect Immun 83:1078-88

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