Instituto de Hortofruticultura Subtropical y Mediterránea "La Mayora", Universidad de Málaga Consejo Superior de Investigaciones Científicas (IHSM-UMA-CSIC), Departamento de Microbiología, Universidad de Málaga, Málaga, Spain.
University of Tuebingen, CMFI Cluster of Excellence, Interfaculty Institute of Microbiology and Infection Medicine, Tuebingen, Germany.
Commun Biol. 2024 Oct 3;7(1):1253. doi: 10.1038/s42003-024-06947-3.
Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes.
生物活性代谢产物在塑造不同生物之间的相互作用方面起着至关重要的作用。在这项研究中，我们鉴定出环（脯氨酸-酪氨酸）是一种由枯草芽孢杆菌产生的代谢产物，它是一种有效的灰葡萄孢和秀丽隐杆线虫的抑制剂，这两种都是潜在的共栖真核生物。根据我们的研究，环（脯氨酸-酪氨酸）破坏质膜极化，诱导氧化应激并增加膜流动性，从而损害真菌膜的完整性。环（脯氨酸-酪氨酸）诱导的这些细胞学和生理学变化可能是由于破坏了含有[H]ATPase Pma1 的膜微区引起的。真菌细胞对环（脯氨酸-酪氨酸）应激作出反应，激活转录组和代谢组应答，主要涉及脂质代谢和活性氧（ROS）解毒，以减轻膜损伤。秀丽隐杆线虫也出现了类似的反应，表明环（脯氨酸-酪氨酸）靶向真核细胞膜。
