イツミ　モモエ   逸見　百江    所属   川崎医科大学  医学部 一般教養　自然科学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Inflammasome regulation by the cell surface ecto-5'-nucleotidase of the oral commensal, Streptococcus oralis.
掲載誌名	正式名：Biochemical and biophysical research communications 略　 称：Biochem Biophys Res Commun ISSNコード：10902104/0006291X
掲載区分	国外
巻・号・頁	744,pp.151206
著者・共著者	Natsuno Nakamura, Hirobumi Morisaki, Momoe Itsumi, Nobuo Okahashi, Haruka Fukamachi, Ayako Sato, Miki Kadena, Mariko Kikuchi, Shohei Matsui, Takahiro Funatsu, Hirotaka Kuwata
発行年月	2025/01
概要	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.
DOI	10.1016/j.bbrc.2024.151206
PMID	39719768