Iatsenko Igor, Yim Joshua J, Schroeder Frank C, Sommer Ralf J
Department of Evolutionary Biology, Max Planck Institute for Developmental Biology, Spemannstraße 37, 72076 Tübingen, Germany.
Department of Evolutionary Biology, Max Planck Institute for Developmental Biology, Spemannstraße 37, 72076 Tübingen, Germany; Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Curr Biol. 2014 Nov 17;24(22):2720-7. doi: 10.1016/j.cub.2014.09.055. Epub 2014 Nov 6.
Studies on Caenorhabditis elegans have provided detailed insight into host-pathogen interactions. Usually, the E. coli strain OP50 is used as food source for laboratory studies, but recent work has shown that a variety of bacteria have dramatic effects on C. elegans physiology, including immune responses. However, the mechanisms by which different bacteria impact worm resistance to pathogens are poorly understood. Although pathogen-specific immune priming is often discussed as a mechanism underlying such observations, interspecies microbial antagonism might represent an alternative mode of action. Here, we use several natural Bacillus strains to study their effects on nematode survival upon pathogen challenge. We show that B. subtilis GS67 persists in the C. elegans intestine and increases worm resistance to Gram-positive pathogens, suggesting that direct inhibition of pathogens might be the primary protective mechanism. Indeed, chemical and genetic analyses identified the lipopeptide fengycin as the major inhibitory molecule produced by B. subtilis GS67. Specifically, a fengycin-defective mutant of B. subtilis GS67 lost inhibitory activity against pathogens and was unable to protect C. elegans from infections. Furthermore, we found that purified fengycin cures infected worms in a dose-dependent manner, indicating that it acts as an antibiotic. Our results reveal a molecular mechanism for commensal-mediated C. elegans protection and highlight the importance of interspecies microbial antagonism for the outcome of animal-pathogen interactions. Furthermore, our work strengthens C. elegans as an in vivo model to reveal protective mechanisms of commensal bacteria, including those relevant to mammalian hosts.
对秀丽隐杆线虫的研究为宿主 - 病原体相互作用提供了详细的见解。通常，大肠杆菌菌株OP50用作实验室研究的食物来源，但最近的研究表明，多种细菌对秀丽隐杆线虫的生理机能有显著影响，包括免疫反应。然而，不同细菌影响线虫对病原体抵抗力的机制尚不清楚。尽管病原体特异性免疫启动常被认为是这些观察结果背后的一种机制，但种间微生物拮抗作用可能代表了另一种作用模式。在这里，我们使用几种天然芽孢杆菌菌株来研究它们在病原体攻击下对秀丽隐杆线虫存活的影响。我们发现枯草芽孢杆菌GS67能在秀丽隐杆线虫肠道中持续存在，并增强线虫对革兰氏阳性病原体的抵抗力，这表明直接抑制病原体可能是主要的保护机制。事实上，化学和遗传学分析确定脂肽丰原素是枯草芽孢杆菌GS67产生的主要抑制分子。具体而言，枯草芽孢杆菌GS67的丰原素缺陷型突变体失去了对病原体的抑制活性，并且无法保护秀丽隐杆线虫免受感染。此外，我们发现纯化的丰原素能以剂量依赖的方式治愈受感染的线虫，这表明它起到了抗生素的作用。我们的研究结果揭示了共生菌介导的秀丽隐杆线虫保护的分子机制，并突出了种间微生物拮抗作用对动物 - 病原体相互作用结果的重要性。此外，我们的工作强化了秀丽隐杆线虫作为一种体内模型来揭示共生菌保护机制的作用，包括那些与哺乳动物宿主相关的机制。
