Functional analysis of type III effectors involved in the induction of T3SS-2-dependent inflammation in Salmonella

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07543
• 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: Kitasato University
• Principal Investigator: Haneda Takeshi 北里大学, 薬学部, 講師 (00348591)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: サルモネラ / 腸炎 / III型分泌機構 / エフェクター

Outline of Final Research Achievements

Salmonella enterica serovar Typhimurium (S. Typhimurium) encodes type III secretion systems (T3SS) -1 for epithelial invasion and T3SS-2 for survival in tissue. T3SS-2 injects the effector proteins SifA, SpvB, SseF, SseJ, and SteA into macrophages to trigger cell death through an unknown mechanism. We have shown that Caspase-11 contributes to T3SS-2-dependent cell death in macrophage-like cells. In this study, we indicate that the effector O induces Caspase-11-dependent non-canonical pyroptosis. In contrast, the effector O also triggered a caspase-11-independent cell death pathway. Furthermore, the effector O was required for caspase-11-dependent growth of S. Typhimurium in the colon contents, mesenteric lymph node, and spleen of mice. These data implicate the O as the main T3SS-2 effector protein involved in triggering macrophage cell death and one of the effector proteins aiding survival in tissue.

Free Research Field

細菌感染

Academic Significance and Societal Importance of the Research Achievements

本研究課題で注目したOを含む5つのエフェクターはサルモネラがマクロファージに食菌された際に形成される小胞（Salmonella containing vacuole; SCV）の形成に関わると報告されている。このように病原体がマクロファージ内で特異的な小胞を形成することは、レジオネラ、ブルセラ、または結核菌などの細胞内寄生細菌の感染戦略として知られている。つまり、本研究により明らかにされる炎症誘導機構は、その波及効果として、サルモネラだけではなく、他の病原細菌の病原性解明の重要な情報となる。