The chemical and genetic basis of interspecies interactions

描述（由申请人提供）： 枯草芽孢杆菌产生广泛的细胞外代谢产物，可以抑制细菌和真菌的生长或改变它们的行为，以减弱潜在危险的邻居产生的抗菌产品。我们在这里建议使用成像质谱和经典的分析化学的新技术，系统地确定B的细胞外代谢物组。枯草杆菌，重点是表征由其他细菌物种诱导的相互作用代谢组。我们将研究这些化合物在B相互作用的两种不同结果中所起的作用。枯草杆菌与其他物种。第一种是僵局，其中B。枯草杆菌与产生多种抗菌化合物的其它物种（例如铜绿假单胞菌）形成紧密邻接的菌落。第二，更频繁的行为是接触依赖捕食，其中B。枯草芽孢杆菌向邻近菌落移动，侵入并破坏邻近菌落，导致被捕食物种的死亡并扩大B的领地。枯草菌菌落这些繁殖行为在不同的未驯化的B中是保守的。枯草杆菌菌株我们将确定这些行为是否依赖于相互作用的代谢组，并研究单个化合物对靶细胞活力和行为的影响。我们将进一步研究种间相互作用的遗传要求，以确定有助于这些不同结果的应激反应，发育和生物合成途径，我们将使用荧光显微镜来可视化种间相互作用的细胞后果。这些研究将阐明种间相互作用的机制基础，并确定影响其他代表潜在新抗菌药物的物种的生存能力或行为的次级代谢产物。 公共卫生相关性： 细菌产生许多介导其与其他物种相互作用的胞外代谢物，其中许多具有抗细菌和抗真菌活性。我们将在这里阐明这些分子使枯草芽孢杆菌与其他细菌物种相互作用的化学，遗传和细胞机制，产生从共存到入侵和破坏相邻菌落的结果。物种间的相互作用在医学上是至关重要的，促进其他物种破坏的代谢物代表了有前途的新的药物线索。

DESCRIPTION (provided by applicant): Bacillus subtilis produces a wide array of extracellular metabolites that can inhibit the growth of bacteria and fungi or modify their behavior to attenuate the production of antibacterial products by potentially dangerous neighbors. We here propose to use the new technique of imaging mass spectrometry and classical analytical chemistry to systematically identify the extracellular metabolome of B. subtilis, with a focus on characterizing the interactive metabolome that is induced by other bacterial species. We will investigate the role these compounds play in two distinct outcomes of the interaction of B. subtilis with other species. The first is an impasse, in which B. subtilis forms closely abutting colonies with other species that produce a variety of antibacterial compounds (such as P. aeruginosa). The second, more frequent behavior is contact-dependent predation, in which B. subtilis moves towards, invades and destroys neighboring colonies, leading to death of the prey species and expanding the territory of the B. subtilis colony. These reproducible behaviors are conserved in different undomesticated B. subtilis strains. We will determine if these behaviors depend on the interactive metabolome and investigate the effects individual compounds have on target cell viability and behavior. We will further investigate the genetic requirements for interspecies interactions to identify stress responses, developmental and biosynthetic pathways that contribute to these distinct outcomes and we will use fluorescence microscopy to visualize the cellular consequences of interspecies interactions. These studies will illuminate the mechanistic basis for interspecies interactions and identify secondary metabolites that affect viability or behavior of other species that represent potential new antibacterial drugs. PUBLIC HEALTH RELEVANCE: Bacteria produce many extracellular metabolites that mediate their interaction with other species, many of which have antibacterial and antifungal activities. We will here elucidate the chemical, genetic and cellular mechanisms by which these molecules allow Bacillus subtilis to interact with other bacterial species, producing outcomes ranging from coexistence to the invasion and destruction of neighboring colonies. Interspecies interactions are critical in medicine and the metabolites that facilitate destruction of other species represent promising new pharmaceutical leads.