Streptococcus suis 5'-nucleotidases contribute to adenosine-mediated immune evasion and virulence in a mouse model.

Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101531386 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-5608 (Electronic) Linking ISSN: 21505594 NLM ISO Abbreviation: Virulence Subsets: MEDLINE

Publication: 2015- : Philadelphia, PA : Taylor & Francis
Original Publication: Austin, Tex. : Landes Bioscience

Streptococcus suis*/pathogenicity ; Streptococcus suis*/enzymology ; Streptococcus suis*/immunology ; Streptococcus suis*/genetics ; 5'-Nucleotidase*/genetics ; 5'-Nucleotidase*/immunology ; 5'-Nucleotidase*/metabolism ; Adenosine*/metabolism ; Streptococcal Infections*/microbiology ; Streptococcal Infections*/immunology ; Disease Models, Animal* ; Immune Evasion*; Animals ; Mice ; Virulence ; Female ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Proteins/immunology ; Neutrophils/immunology ; Neutrophils/microbiology ; Mice, Inbred BALB C ; Substrate Specificity

Streptococcus suis ( S. suis ) is an important swine bacterial pathogen and causes human infections, leading to a wide range of diseases. However, the role of 5'-nucleotidases in its virulence remains to be fully elucidated. Herein, we identified four cell wall-anchored 5'-nucleotidases (Snts) within S. suis , named SntA, SntB, SntC, and SntD, each displaying similar domains yet exhibiting low sequence homology. The malachite green reagent and HPLC assays demonstrated that these recombinant enzymes are capable of hydrolysing ATP, ADP, and AMP into adenosine (Ado), with the hierarchy of catalytic efficiency being SntC>SntB>SntA>SntD. Moreover, comprehensive enzymatic activity assays illustrated slight variances in substrate specificity, pH tolerance, and metal ion requirements, yet highlighted a conserved substrate-binding pocket, His-Asp catalytic dyad, metal, and phosphate-binding sites across Snts, with the exception of SntA. Through bactericidal assays and murine infection assays involving in site-mutagenesis strains, it was demonstrated that SntB and SntC collaboratively enhance bacterial survivability within whole blood and polymorphonuclear leukocytes (PMNs) via the Ado-A2aR pathway in vitro , and within murine blood and organs in vivo . This suggests a direct correlation between enzymatic activity and enhancement of bacterial survival and virulence. Collectively, S. suis 5'-nucleotidases additively contribute to the generation of adenosine, influencing susceptibility within blood and PMNs, and enhancing survival within blood and organs in vivo . This elucidation of their integral functions in the pathogenic process of S. suis not only enhances our comprehension of bacterial virulence mechanisms, but also illuminates new avenues for therapeutic intervention aimed at curbing S. suis infections.

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Keywords: 5’-nucleotidases; Streptococcus suis; adenosine pathway; enzymatic activity; virulence factors

EC 3.1.3.5 (5'-Nucleotidase)
K72T3FS567 (Adenosine)
0 (Bacterial Proteins)

Date Created: 20240916 Date Completed: 20240916 Latest Revision: 20240919

20240919

PMC11407386

10.1080/21505594.2024.2401963

39282964