Streptococcal translocation across epithelial barrier via tricellular junction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Osaka University
• Principal Investigator: Sumitomo Tomoko 大阪大学, 歯学研究科, 講師 (50423421)
• Co-Investigator(Kenkyū-buntansha): 川端 重忠 大阪大学, 歯学研究科, 教授 (50273694) ; 中田 匡宣 大阪大学, 歯学研究科, 准教授 (90444497) ; 山口 雅也 大阪大学, 歯学研究科, 助教 (00714536)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: レンサ球菌 / 上皮バリア

Outline of Final Research Achievements

Streptococcus pyogenes is responsible for a wide variety of cutaneous infections ranging from superficial impetigo to fulminant invasive necrotizing fasciitis. Dysfunction of desmosomes is associated with the pathogenesis of cutaneous diseases. We identified streptococcal pyrogenic exotoxin B (SpeB) as a proteolytic factor that cleaves the extracellular domains of desmoglein 1 and 3. In an epicutaneous infection model, lesional skin infected with an speB deletion mutant were significantly smaller as compared to those caused by the wild-type strain. Our findings provide evidence that SpeB-mediated degradation of desmosomes has a pathogenic role in development of S. pyogenes cutaneous infection. Furthermore, we found that that interaction of HtpA with LSR, a major component of tricellular junctions, is crucial for bacterial localization. Our data suggest that S. pyogenes exploits host LSR for acceleration of bacterial invasion into deeper tissues via tricellular junctions.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

トリセルラージャンクションは上皮バリアの機能維持に必須であるだけでなく，菌感染部位への白血球の遊走ルートでもある．そのため，トリセルラージャンクションの破綻は病態発症や重症化に密接に関連すると推察される．本研究では，化膿レンサ球菌によるトリセルラージャンクションの機能障害と病態形成の関連を明らかにした．今後，LSRを介したトリセルラージャンクションの破綻に繋がるシグナル伝達経路が明らかになれば，劇症型レンサ球菌感染症だけでなく他の病原性レンサ球菌による感染症や類似病態を呈する感染症の新たな治療法や感染防御法の確立に繋がると考える．