Clash of the Kingdoms: How the quest for nutrients leads to pathogenicity

链霉菌是一种无害的土壤细菌，通常在植物根部周围发现，与植物相互作用，但不会引起疾病。链霉菌还与其他土壤生物相互作用，如阿米巴，单细胞生物的行为类似于人体内的吞噬细胞，吃细菌细胞。目前，我们对这些不同物种如何在分子水平上相互作用知之甚少。最近，我们能够识别出一组基因(mce基因，代表哺乳动物细胞进入基因)，这些基因在链霉菌中发现，并且与其远亲结核分枝杆菌的基因关系非常密切，结核杆菌是导致结核病的细菌。我们证明了这些基因编码一个运输系统，对于链霉菌从植物根中收集营养以及与阿米巴相互作用是重要的。然而，在结核分枝杆菌中，它们需要它们来定植人类肺细胞并在这些细胞内生长。在这项提案中，我们将全面描述这种运输系统，并研究这些基因编码的蛋白质的分子细节，包括它们结合和吸收的底物，以及它们对植物和阿米巴在物理和遗传上的影响。这项研究的发现将对我们理解人类和动物病原体是如何从非致病细菌进化而来的，以及细菌如何能够在植物上定居并与植物病原体竞争以阻止它们致病。这些基因也有可能用于生物技术行业，帮助制造有用的药物，如从植物废物中提取类固醇。

Streptomyces is a harmless soil bacterium that is often found around the roots of plants, interacting with them but without causing disease. Streptomyces also interacts with other soil organisms such as amoeba, single celled organisms that behave like the phagocytic cells in the human body, eating bacterial cells. Currently we know very little about how these different species interact at the molecular level. Recently we were able to identify that a group of genes (the mce genes, which stands for Mammalian Cell Entry genes)that are found in Streptomyces and are very closely related to genes in its distant cousin Mycobacterium tuberculosis, the bacterium that causes TB. We showed that these genes encode a transport system and are important for Streptomyces to gather nutrients from plant roots and also to interact with the amoebae. Yet in M. tuberculosis they are required for them to colonise human lung cells and grow within those cells. In this proposal we will fully characterise this transport system and study the molecular details of what the proteins encoded by these genes do, what substrates they bind and take up, and what effect they have on plant and amoeba both physically and also genetically. The findings of this study will have implications for our understanding of how human and animal pathogens have evolved from non-pathogenic bacteria and how bacteria can colonise plants and out-compete plant pathogens to stop them from causing disease. There are also possibilities that these genes can be used in the biotechnology industry to help make useful drugs, such as steroids from plant waste products.