The Impact of Horizontal Gene Transfer on Bacterial Warfare

如果我们想要了解和操纵重要的微生物生态系统，如人类肠道微生物组，研究细菌与其他细菌的相互作用是至关重要的。我们知道，这些微生物群落经常充满冲突，因为许多细菌参与细菌间的战争，并用复杂的分子武器杀死竞争对手的细菌。但其中一些武器会带来潜在的负面影响。它们被编码在可以在细胞之间移动的基因上，因此携带它们的细菌有可能为附近的竞争对手提供自己的武器。虽然众所周知，分子武器可能是谁在细菌群落中生存的关键决定因素，但武器基因在细菌之间传递的影响在很大程度上还没有被探索。我将利用了解细菌生物学的主要模式生物之一-人类肠道微生物大肠杆菌-来填补这一空白。大肠杆菌非常适合研究武器基因的流动性，因为它们有许多描述良好的分子武器，其基因可以转移，而且很容易进行基因操作。利用这些携带武器的大肠杆菌，我将解决细菌战研究中的三个主要悬而未决的问题：1)武器传播如何影响细菌战？2)移动武器基因有时会以牺牲细菌宿主的利益为代价进行自我繁殖吗？以及3)移动武器基因决定了哪些细菌可以入侵微生物肠道群落吗？在牛津大学，我将把基因工程和尖端显微镜结合起来，可视化和研究在细菌之间移动的武器基因，并建立一个重大的新研究计划，以了解微生物生命中这一重要而迷人的方面的关键方面。

Examining how bacteria interact with other bacteria is crucial if we want to understand and manipulate important microbial ecosystems such as the human gut microbiome. We know that these microbial communities are often rife with conflict, as many bacteria engage in inter-bacterial warfare and kill competing bacteria with sophisticated molecular weaponry. But some of these weapons entail a potential downside. They are encoded on genes that can move between cells, and the bacteria carrying them thus run the risk of providing nearby competitors with their own weapon. While it is known that molecular weapons can be key determinants for who survives in bacterial communities, the effects of weapon genes being passed between bacteria are largely unexplored. I will fill this gap by making use of one of the major model organisms for understanding bacterial biology - the human gut microbe Escherichia coli.E. coli bacteria are ideally suited for studying weapon gene mobility as they have many well-described molecular weapons whose genes can be transferred, and they are easy to genetically manipulate. Using these weapon-carrying E. coli bacteria, I will tackle three major open questions in the study of bacterial warfare: 1) How does weapon transmission impact bacterial battles? 2) Are mobile weapon genes sometimes self-serving by propagating themselves at the expense of their bacterial hosts? and 3) Do mobile weapon genes determine which bacteria can invade a microbial gut community?At the University of Oxford, I will combine genetic engineering with cutting-edge microscopy to visualize and study weapon genes moving between bacteria, and establish a major new research program to understand key aspects of this important and fascinating aspect of microbial life.