Abstract

Morbidity and mortality of human newborns remain significant public health concerns. Streptococcus agalactiae or Group B Streptococcus (GBS) cause invasive infections such as pneumonia, sepsis and meningitis in human newborns. Moreover, GBS are a significant cause of in utero infections leading to preterm births and stillbirths. We recently showed that the pluripotent toxin important for GBS infections is an ornithine rhamnolipid pigment also known as granadaene. The pigment/lipid toxin is cytotoxic to a number of host cells and induces a proinflammatory immune response. The objective of this proposal is to understand how the pigment causes host cell lysis and induces an immune response and to also define how pigment mediated activation of host cells affects GBS colonization and infection-associated preterm births.

Public Health Relevance

Understanding how the pigment/lipid toxin activates an immune response and causes host cell lysis will be valuable for the development of therapeutic strategies that prevent Group B Streptococcal infections in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI112619-04
Application #
9297204
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
GU, Xin-Xing
Project Start
2014-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98101

  Publications

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
Vornhagen, Jay; Quach, Phoenicia; Santana-Ufret, Verónica 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
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
Gendrin, Claire; Vornhagen, Jay; Armistead, Blair et al. (2018) A Nonhemolytic Group B Streptococcus Strain Exhibits Hypervirulence. J Infect Dis 217:983-987
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
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
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

Showing the most recent 10 out of 15 publications