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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI112619-01
Application #
8745832
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
GU, Xin-Xing
Project Start
2014-07-01
Project End
2019-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
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
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
Gendrin, Claire; Shubin, Nicholas J; Boldenow, Erica et al. (2017) Mast cell chymase decreases the severity of group B Streptococcus infections. J Allergy Clin Immunol :
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:
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:
McAdams, Ryan M; Bierle, Craig J; Boldenow, Erica et al. (2015) Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina. Infect Immun 83:3909-17
Adams Waldorf, Kristina M; Singh, Natasha; Mohan, Aarthi R et al. (2015) Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates. Am J Obstet Gynecol 213:830.e1-830.e19
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
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 11 publications