title: Interaction of factor H-binding protein of Streptococcus suis with globotriaosylceramide promotes the development of meningitis.
abstract: Streptococcus suis is an important emerging zoonotic agent that causes acute bacterial meningitis in humans with high mortality and morbidity. Our previous work showed that factor H-binding protein (Fhb) contributed to virulence of S. suis, but the role of Fhb in the development of S. suis meningitis remained unclear. In this study, we demonstrated for the first time that Fhb contributed to the traversal of S. suis across the human blood-brain barrier by allelic-exchange mutagenesis, complementation and specific antibody blocking studies. We also showed that globotriaosylceramide (Gb3), the receptor of Fhb, was involved in this process and affected S. suis infection-induced activation of myosin light chain 2 through Rho/ROCK signaling in hCMEC/D3 cells. Using a murine model of S. suis meningitis, we further demonstrated that Gb3-deficiency prevented the mice from developing severe brain inflammation or injury. Our results demonstrate that the Fhb-Gb3 interaction plays an important role in the development of S. suis meningitis and might be a potential therapeutic target against S. suis infection.
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Decong
authors.initials: D
authors.lastname: Kong
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.|b College of Biological Science & Technology , Shenyang Agricultural University , Shenyang , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.|d Urumqi Ethnic Cadres' College , Urumqi , China.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Lv
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Maokai
authors.initials: M
authors.lastname: Xu
authors.affiliation: c CAS Key Laboratory of Pathogenic Microbiology and Immunology , Institute of Microbiology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: c CAS Key Laboratory of Pathogenic Microbiology and Immunology , Institute of Microbiology, Chinese Academy of Sciences , Beijing , China.
authors.forename: Huaijie
authors.initials: H
authors.lastname: Hao
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity , Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing , China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D016920:Meningitis, Bacterial / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013290:Streptococcal Infections / Q000378:metabolism* / Q000382:microbiology; D017011:Streptococcus suis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D014281:Trihexosylceramides / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D014281:Trihexosylceramides; C018549:globotriaosylceramide
keywords: Fhb; Gb3; Streptococcus suis; blood–brain barrier; meningitis