Mechanisms of intracellular bacterial killing induced by reactive sulfur species

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22258
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Sawa Tomohiro 熊本大学, 大学院生命科学研究部(医), 教授 (30284756)
• Co-Investigator(Kenkyū-buntansha): 津々木 博康 熊本大学, 大学院生命科学研究部(医), 助教 (40586608) ; 荒木 令江 熊本大学, 大学院生命科学研究部(医), 准教授 (80253722) ; 小野 勝彦 熊本大学, 大学院生命科学研究部(医), 助教 (80573592)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 食細胞 / 活性イオウ / 細胞内殺菌 / マクロファージ

Outline of Final Research Achievements

Cysteine persulfide and polysulfides are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. This study was conducted to clarify the impact of chemically synthesized polysulfide donors towards bacterial infections. We used N-Acetyl-L-cysteine polysulfide as potent polysulfide donors. Immune cells were infected with Salmonella enterica serovar Typhimurium LT2. Extracellular bacteria were killed by using gentamycin. NAC polysulfides were added into infected-cells during gentamycin treatment. Treatment of NAC polysulfides remarkably decreased intracellular bacterial numbers. NAC polysulfides-enhanced bacterial killing was not ascribed to increased productions of nitric oxide, cytokines, and reactive oxygen species, suggesting a non-canonical bacterium killing route. Precise understanding of mechanisms by which NAC polysulfides-mediated bacterial killing in immune cells may be helpful to develop therapeutic strategies for bacterial infectious diseases.

Free Research Field

細菌学、生化学

Academic Significance and Societal Importance of the Research Achievements

今回、活性イオウドナーの作用により、感染にともなう活性酸素を消去しながら、一方で活性酸素の殺菌作用とは全く異なる機構で細胞内の細菌を排除している可能性を強く示唆する結果を得た。今後、より積極的に活性イオウを増やすことで、特に免疫力の低下した宿主に対する新しい感染予防あるいは治療の補助方法としての展開も期待される。具体的には含硫食品（卵、緑色野菜など）の摂取や、運動によるミトコンドリア量の増加による感染予防効果の検証などが含まれる。活性イオウドナーを従来の抗菌剤と併用することでより効果的な殺菌治療への展開も期待される。