Inflammasome regulation by the cell surface ecto-5'-nucleotidase of the oral commensal, Streptococcus oralis

Natsuno Nakamura; Hirobumi Morisaki; Momoe Itsumi; Nobuo Okahashi; Haruka Fukamachi; Ayako Sato; Miki Kadena; Mariko Kikuchi; Shohei Matsui; Takahiro Funatsu; Hirotaka Kuwata

doi:10.1016/j.bbrc.2024.151206

Inflammasome regulation by the cell surface ecto-5'-nucleotidase of the oral commensal, Streptococcus oralis

Biochem Biophys Res Commun. 2024 Dec 19:744:151206. doi: 10.1016/j.bbrc.2024.151206. Online ahead of print.

Authors

Affiliations

¹ Department of Oral Microbiology and Immunology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan; Department of Dentistry for Persons with Disabilities, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
² Department of Oral Microbiology and Immunology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan. Electronic address: morisaki@dent.showa-u.ac.jp.
³ Department of Oral Microbiology and Immunology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan.
⁴ Department of Oral Microbiology and Immunology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan; Department of Perioperative Medicine, Division of Medical and Dental Cooperative Dentistry, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
⁵ Department of Dentistry for Persons with Disabilities, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
⁶ Department of Perioperative Medicine, Division of Medical and Dental Cooperative Dentistry, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
⁷ Department of Dentistry for Persons with Disabilities, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan; Department of Pediatric Dentistry, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.
⁸ Department of Oral Microbiology and Immunology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan. Electronic address: hkuwata@dent.showa-u.ac.jp.

PMID: 39719768
DOI: 10.1016/j.bbrc.2024.151206

Abstract

Streptococcus oralis is a commensal oral bacterium that acts as an opportunistic pathogen, causing systemic diseases, such as infective endocarditis and aspiration pneumonia. However, the specific molecular mechanisms underlying its transition from commensal to pathogenic state remain unclear. In this study, to further elucidate the mechanisms underlying virulence expression, we identified and characterized the cell surface-associated ecto-5'-nucleotidase (Nt5e) in S. oralis. Biochemical analysis revealed Nt5e as a metal-dependent enzyme dephosphorylating ATP and producing adenosine, an immunosuppressive molecule that inhibits macrophage activation. Additionally, Nt5e was a critical regulator of innate immunity, particularly inflammasome activation, via environmental ATP metabolism. Analysis of an isogenic nt5e deletion mutant and its complemented strain revealed that cell surface-associated Nt5e played a crucial role in degrading extracellular ATP. The Nt5e-orchestrated mechanism possibly maintained the host-bacteria homeostasis under normal conditions, whereas its dysregulation facilitated pathogenicity in specific circumstances. Our study provides new insights into the mechanisms by which oral commensals modulate host immune responses and highlights Nt5e as a potential therapeutic target for S. oralis-associated systemic diseases.

Keywords: 5′-nucleotidase; ATP metabolism; Host–bacteria homeostasis; Immune regulation; Inflammasome; Oral microbiota; Streptococcus oralis.