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Citation
Chang, Y.C., Wang, Z., Flax, L.A., Xu, D., Esko, J.D., Nizet, V., Baron, M.J. (2011). Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems.  PLoS Pathog. 7(6): e1002082.
FlyBase ID
FBrf0214234
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC3121876 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Pathog.
    Title
    PLoS Pathogens
    Publication Year
    2005-
    ISBN/ISSN
    1553-7366 1553-7374
    Data From Reference
    Genes (7)