title: Mechanisms of Host-Pathogen Protein Complex Formation and Bacterial Immune Evasion of Streptococcus suis Protein Fhb.
abstract: Streptococcus suis serotype 2 (S. suis 2)-induced sepsis and meningitis are often accompanied by bacteremia. The evasion of polymorphonuclear leukocyte-mediated phagocytic clearance is central to the establishment of bacteremia caused by S. suis 2 and is facilitated by the ability of factor H (FH)-binding protein (Fhb) to bind FH on the bacterial surface, thereby impeding alternative pathway complement activation and phagocytic clearance. Here, C3b/C3d was found to bind to Fhb, along with FH, forming a large immune complex. The formation of this immune complex was mediated by domain II of Fhb via electrostatic and hydrophobic interactions, which, to our knowledge, is a new type of interaction. Interestingly, Fhb was found to be associated with the cell envelope and also present in the culture supernatant, where secreted Fhb inhibited complement activation via interactions with domain II, thereby enhancing antiphagocytic clearance by polymorphonuclear leukocytes. Thus, Fhb is a multifunctional bacterial protein, which binds host complement component C3 as well as FH and interferes with innate immune recognition in a secret protein manner. S. suis 2 therefore appears to have developed a new strategy to combat host innate immunity and enhance survival in host blood.
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and the Central Laboratory of Yijishan Hospital, Wannan Medical College, Wuhu 241001, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Gan
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and.
authors.forename: Chunmao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and jiangyq@nic.bmi.ac.cn.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: From the State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071 and miniminiyuan@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D015933:Complement C3d / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007962:Leukocytes / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology*; D017011:Streptococcus suis / Q000472:pathogenicity* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D003179:Complement C3b; D015933:Complement C3d; D017242:Complement Factor H
keywords: Factor H;complement 3; Fhb; Streptococcus; Streptococcus suis; complement; host defense; immune evasion; infection; secretion; streptococcus; streptococcus suis