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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, Bacterial / chemistry
-
Antigens, Bacterial / genetics
-
Antigens, Bacterial / metabolism*
-
Antigens, Bacterial / toxicity
-
Bacterial Proteins / chemistry
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism*
-
Bacterial Proteins / toxicity
-
Binding Sites
-
Cell Aggregation / drug effects
-
Cloning, Molecular
-
Escherichia coli / genetics
-
Escherichia coli / metabolism
-
Fibrinogen / chemistry
-
Fibrinogen / genetics
-
Fibrinogen / metabolism*
-
Gene Expression
-
Genetic Vectors / chemistry
-
Genetic Vectors / metabolism
-
Humans
-
Integrin alphaXbeta2 / genetics*
-
Integrin alphaXbeta2 / immunology
-
Microbial Viability
-
Neutrophils / drug effects
-
Neutrophils / immunology
-
Neutrophils / microbiology
-
Protein Binding
-
Protein Conformation, alpha-Helical
-
Protein Conformation, beta-Strand
-
Protein Interaction Domains and Motifs
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Streptococcal Infections / immunology
-
Streptococcal Infections / microbiology
-
Streptococcus suis / genetics*
-
Streptococcus suis / isolation & purification
-
Streptococcus suis / metabolism
-
Streptococcus suis / pathogenicity
-
Swine
-
Virulence Factors / chemistry
-
Virulence Factors / genetics
-
Virulence Factors / metabolism*
-
Virulence Factors / toxicity
Substances
-
Antigens, Bacterial
-
Bacterial Proteins
-
Integrin alphaXbeta2
-
MRP protein, Streptococcus suis
-
Recombinant Proteins
-
Virulence Factors
-
Fibrinogen