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

Authors :
Simin Deng
Haojie Li
Chang Zhou
Jingyan Fan
Fuxin Zhu
Gexuan Jin
Jiali Xu
Jing Xia
Jing Wang
Zheng Nie
Rui Zhou
Houhui Song
Changyong Cheng
Source :
Virulence, Vol 15, Iss 1 (2024)
Publication Year :
2024
Publisher :
Taylor & Francis Group, 2024.

Abstract

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.

Details

Language :
English
ISSN :
21505594 and 21505608
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Virulence
Publication Type :
Academic Journal
Accession number :
edsdoj.b7acc77254a4004b4dcc9fa0560b0a3
Document Type :
article
Full Text :
https://doi.org/10.1080/21505594.2024.2401963