Analysis of host control mechanism by novel function of Nga, a secreted toxin of group A Streptococcus

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07023
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kyoto University
• Principal Investigator: Nozawa Takashi 京都大学, 医学研究科, 准教授 (10598858)
• Co-Investigator(Kenkyū-buntansha): 相川 知宏 京都大学, 医学研究科, 助教 (70725499)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: A群レンサ球菌 / 分泌毒素 / ストレス応答 / ストレス顆粒

Outline of Final Research Achievements

The aim of this study was to elucidate the molecular mechanism of host regulation by Nga, a secreted toxin of group A Streptococcus, and to reveal a novel mechanism of virulence exerted by group A Streptococcus. Genome-wide screening revealed that Nga induces stress granule formation via the integrated stress response (ISR). Furthermore, proteomic analysis of stress granules revealed that the ER-Golgi transport pathway mediated by proteotoxic stress is disrupted, leading to Golgi fragmentation. Golgi fragmentation resulted in the disruption of various immune functions such as chemokine secretion, epithelial cell layer homeostasis, and antigen presentation pathways. These results reveal a mechanism of pathogenicity exerted by the secreted toxin Nga through the host stress responses.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

A群レンサ球菌による劇症型感染症は国内でも年々増加しており、本菌の病原性発揮機序の解明は学術的だけでなく社会的意義も大きい。中でも、本研究で着目した分泌毒素Ngaは、本菌の病原性に密接に関わる毒素であり、この毒素による免疫破綻機構の一端を明らかにできたことは、今後の新規治療法の開発において重要な基盤的知見となると考えている。