Blair Armistead1,2, Phoenicia Quach2, Jessica M Snyder3, Verónica Santana-Ufret2, Anna Furuta1,2, Alyssa Brokaw1,2, Lakshmi Rajagopal1,2,4. 1. Department of Global Health, University of Washington, Seattle, Washington, USA. 2. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA. 3. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA. 4. Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.
Abstract
BACKGROUND: Group B streptococci (GBS) are β-hemolytic, Gram-positive bacteria associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A key factor promoting GBS virulence is the β-hemolysin/cytolysin, a pigmented ornithine rhamnolipid (also known as granadaene) associated with the bacterial surface. METHODS: A previous study indicated that GBS produce small structures known as membrane vesicles (MVs), which contain virulence-associated proteins. In this study, we show that GBS MVs are pigmented and hemolytic, indicating that granadaene is functionally active in MVs. RESULTS: In addition, MVs from hyperhemolytic GBS induced greater cell death of neutrophils, T cells, and B cells compared with MVs from isogenic nonhemolytic GBS, implicating MVs as a potential mechanism for granadaene-mediated virulence. Finally, hemolytic MVs reduced oxidative killing of GBS and aggravated morbidity and mortality of neonatal mice infected with GBS. CONCLUSIONS: These studies, taken together, reveal a novel mechanism by which GBS deploy a crucial virulence factor to promote bacterial dissemination and pathogenesis.
BACKGROUND: Group B streptococci (GBS) are β-hemolytic, Gram-positive bacteria associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A key factor promoting GBS virulence is the β-hemolysin/cytolysin, a pigmented ornithine rhamnolipid (also known as granadaene) associated with the bacterial surface. METHODS: A previous study indicated that GBS produce small structures known as membrane vesicles (MVs), which contain virulence-associated proteins. In this study, we show that GBS MVs are pigmented and hemolytic, indicating that granadaene is functionally active in MVs. RESULTS: In addition, MVs from hyperhemolytic GBS induced greater cell death of neutrophils, T cells, and B cells compared with MVs from isogenic nonhemolytic GBS, implicating MVs as a potential mechanism for granadaene-mediated virulence. Finally, hemolytic MVs reduced oxidative killing of GBS and aggravated morbidity and mortality of neonatal mice infected with GBS. CONCLUSIONS: These studies, taken together, reveal a novel mechanism by which GBS deploy a crucial virulence factor to promote bacterial dissemination and pathogenesis.
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