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Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems
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نویسنده
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chang y.-c. ,wang z. ,flax l.a. ,xu d. ,esko j.d. ,nizet v. ,baron m.j.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 6
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چکیده
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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. © 2011 chang et al.
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آدرس
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glycobiology research and training center,university of california,san diego,la jolla,ca,united states,department of pediatrics,university of california,san diego,la jolla,ca, United States, channing laboratory,brigham and women's hospital,boston,ma,united states,children's hospital,boston,ma, United States, channing laboratory,brigham and women's hospital,boston,ma, United States, glycobiology research and training center,university of california,san diego,la jolla,ca,united states,department of cellular and molecular medicine,university of california,san diego,la jolla,ca, United States, glycobiology research and training center,university of california,san diego,la jolla,ca,united states,department of cellular and molecular medicine,university of california,san diego,la jolla,ca, United States, glycobiology research and training center,university of california,san diego,la jolla,ca,united states,department of pediatrics,university of california,san diego,la jolla,ca,united states,skaggs school of pharmacy and pharmaceutical sciences,university of california,san diego,la jolla,ca,united states,rady children's hospital,san diego,ca, United States, channing laboratory,brigham and women's hospital,boston,ma,united states,harvard medical school,boston,ma, United States
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Authors
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