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，与它们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，如变形虫，单细胞生物，其行为类似于人体中的吞噬细胞，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，我们能够鉴定出一组在链霉菌中发现的基因（mce基因，代表哺乳动物细胞进入基因），它们与其远亲结核分枝杆菌（导致结核病的细菌）中的基因非常密切相关。我们发现，这些基因编码一个运输系统，是重要的链霉菌从植物根部收集养分，也与变形虫。然而在M.结核病需要它们来定殖人类肺细胞并在这些细胞内生长。在这个提议中，我们将充分研究这个运输系统，并研究这些基因编码的蛋白质的分子细节，它们结合和吸收什么底物，以及它们对植物和变形虫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如何从非致病性细菌进化以及细菌如何能够殖民植物并与植物病原体竞争以阻止它们引起疾病产生影响。这些基因也有可能用于生物技术工业，以帮助制造有用的药物，例如从植物废料中提取类固醇。

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.