Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems.

Abstract

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications.

• Authors: Yung-Chi Chang, Zhipeng Wang, Lindsay A Flax, Ding Xu, Jeffrey D Esko, Victor Nizet, Miriam J Baron
• Journal: PLoS pathogens (PLoS Pathog) Vol. 7 Issue 6 Pg. e1002082 (Jun 2011) ISSN: 1553-7374 [Electronic] United States
• PMID: 21731486 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Bacterial Proteins
• Glycosaminoglycans
• alpha C protein, group B streptococci

Topics

• Animals
• Antigens, Surface (metabolism)
• Bacterial Infections (etiology, pathology)
• Bacterial Proteins (metabolism)
• Blood-Brain Barrier (microbiology)
• Brain (microbiology)
• Central Nervous System (microbiology)
• Drosophila (microbiology)
• Endothelial Cells (microbiology)
• Endothelium, Vascular (microbiology)
• Glycosaminoglycans (metabolism)
• Humans
• Mice
• Mutagenesis, Site-Directed
• Protein Binding
• Streptococcus agalactiae (pathogenicity)