Elucidation of the mechanism and biological significance of bacterial exit from infected cells during group A streptococcus infection

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16241
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kyoto University
• Principal Investigator: Nozawa Atsuko 京都大学, 医学研究科, 特定助教 (60824159)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: TBC1D18 / RabGAP1L / RHOQ / Rab10 / ARL10 / SLO / Nga / A群レンサ球菌

Outline of Final Research Achievements

Group A Streptococcus (GAS) typically invades epithelial cells and is transported by host membrane trafficking in infected cells. Since we have already revealed the RAB GTPase activating protein 1-like (TBC1D18) regulates exocytic and endocytic trafficking of the invading Group A Streptococcus, the present study aimed to extensively examine interaction factors of TBC1D18 and bacterial factors that are involved in bacterial exit from infected cells during GAS infection.
TBC1D18 interacted with Rab10, RHOQ, and ARL10, respectively. Rab10 and RHOQ regulated endolysosomal trafficking and subsequent autophagy induction and ARL10 regulated exocytic process via endocytic recycling during GAS infection. On the other hand, bacterial secretary protein, SLO and Nga, were required for exocytosis of GAS (bacterial exit from infected cells) through increasing intracellular calcium level. These interaction factors of TBC1D18 and bacterial factors are critical for intercellular trafficking of GAS.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

A群レンサ球菌(GAS)はヒトの咽頭炎や化膿性皮膚感染症などの原因菌としてよくみられる一方で、軟部組織壊死や敗血症性ショックを伴う劇症型レンサ球菌感染症(STSS)が世界各国で報告され、近年、日本においても患者数は増加傾向にある。STSSは発病から病状の進行が急激で、致死率も約30％と高いことから、医学的重要性は極めて高い。今回の結果は、GASの「細胞外脱出」という新概念を介したGASの病態発症機序の解明に繋がり得る知見であり、学術的な観点だけでなく、劇症型溶血性レンサ球菌感染症の治療法開発やワクチン開発に発展する臨床応用に向けた観点からも重要な知見である。