Isolation and identification of a self-growth-inhibiting substance produced by Legionella sp. and its application as an anti-Legionella drug

军团菌产生的自我生长抑制物质的分离和鉴定。

• 批准号: 12556016
• 负责人: SAKUDA Shohei
• 金额: $ 4.29万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12556016/
• 关键词: Legionella species; self-growth-inhibiting substance; sulfur; Legionnaires' disease; Legionella pneumophila

Legionella species, ubiquitous Gram-negative bacteria, are found in natural or man-made water systems. Their natural hosts are probably various amoebae species. If humans inhale aerosolized water from sources contaminated with them, such as cooling towers or whirlpool spas, the bacteria can invade and replicate within alveolar macrophages, causing a severe form of pneumonia called Legionnaires' disease. If the pneumonia is not treated promptly with antibiotics effective against the bacterium, the mortality rate can approach 15-20%. Therefore, control and management of Legionella contamination in some water systems are very important. Activated charcoal is usually added to a medium for the culture of Legionella species to enhance the growth of the bacteria. We found that activated charcoal can be replaced by Diaion HP-20 resin and that methanol extracts of the resins recovered from the culture broth of Legionella pneumophila showed strong growth-inhibitory activity toward the bacterium itself. The growth inhibitor was isolated from the methanol extracts and identified as sulfur. Sulfur was not obtained from the resins in a medium without cultivation of the bacterium, indicating that it was produced endogenously by the bacterium. Sulfur shows strong growth-inhibitory activity toward all Legionella species tested. Our results obtained in this study showed that sulfur may be a good candidate as a drug for preventing Legionella contamination in water systems effectively and cheaply.

军团菌属是一种普遍存在的革兰氏阴性细菌，存在于自然或人造水系统中。它们的自然宿主可能是各种变形虫。如果人类从被污染的来源（如冷却塔或漩涡水疗中心）吸入雾化水，细菌可以侵入肺泡巨噬细胞并在其中复制，导致称为军团病的严重肺炎。如果肺炎没有及时用有效的抗生素治疗，死亡率可接近15- 20%。因此，控制和管理某些水系统中的军团菌污染非常重要。活性炭通常被添加到用于培养军团菌属物种的培养基中，以促进细菌的生长。我们发现，活性炭可以取代Diaion HP-20树脂和从嗜肺军团菌培养液中回收的树脂的甲醇提取物对细菌本身表现出很强的生长抑制活性。从甲醇提取物中分离出生长抑制剂，并鉴定为硫。在没有培养细菌的培养基中，不能从树脂中获得硫，这表明硫是由细菌内源性产生的。硫对所有测试的军团菌属物种显示出强烈的生长抑制活性。我们在这项研究中获得的结果表明，硫可能是一个很好的候选人作为一种药物，用于防止军团菌污染的水系统有效和廉价。