Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI109222-01
Application #
8619390
Study Section
Special Emphasis Panel (ZRG1-IDM-B (80))
Program Officer
GU, Xin-Xing
Project Start
2013-12-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
1
Fiscal Year
2014
Total Cost
$274,156
Indirect Cost
$133,563

  Institution

Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105

  Publications

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
Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo et al. (2018) Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates. Am J Obstet Gynecol 218:438.e1-438.e16
Lannon, Sophia M R; Adams Waldorf, Kristina M; Fiedler, Tina et al. (2018) Parallel detection of lactobacillus and bacterial vaginosis-associated bacterial DNA in the chorioamnion and vagina of pregnant women at term. J Matern Fetal Neonatal Med :1-9
Vornhagen, Jay; Armistead, Blair; Santana-Ufret, Verónica 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

Showing the most recent 10 out of 16 publications