title: Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXβ2 Integrin-dependent Manner.
abstract: The Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283-721) binds to both the Aα and Bβ chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXβ2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia, and these data shed new light on the function of MRP in S. suis pathogenesis.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.|Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101,China.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Pian
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D001665:Binding Sites; D002449:Cell Aggregation / Q000187:drug effects; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics* / Q000276:immunology; D050296:Microbial Viability; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology; D017011:Streptococcus suis / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D013552:Swine; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016167:Integrin alphaXbeta2; C421489:MRP protein, Streptococcus suis; D011994:Recombinant Proteins; D037521:Virulence Factors; D005340:Fibrinogen