From curiosity to curative- developing Bdellovibrio as living antibiotics between farm and fork

蛭弧菌是一种小型的、对人类友好的掠食性细菌，它们侵入其他致病菌的细胞（比如导致人类食物中毒的致病菌）并杀死它们。蛭弧菌对人类、动物或鸟类细胞没有活性，但它们天生擅长杀死其他细菌。致病菌对蛭弧菌的附着和侵袭没有简单的细胞表面受体，因此它们不容易对蛭弧菌产生耐药性（与传统抗生素的情况不同）蛭弧菌于20世纪60年代被发现，最近我们和其他人一直在研究它们的基因，并试图了解它们如何对人类有用。以前的科学家发表过简短的报告，表明蛭形弧菌对农场环境中的一系列食源性病原体具有掠食性活性，但他们通常在食物制备表面（如板或刀）或食物本身进行研究。目前还没有人发表过有关蛭形弧菌治疗农场动物食源性致病菌的数据。这使得蛭弧菌坐在场边与许多报道的潜力作为一种抗菌剂，但没有真正的步骤向前应用它。我们希望在人类致病性沙门氏菌的应用中做到这一点，包括在欧洲、英国和美国导致人类疾病的噬菌体4型肠炎沙门氏菌，以及家禽和鸟类致病性和定植菌株，包括鸡沙门氏菌。我们已经开展了一个小型试点项目，该项目表明，给被沙门氏菌（一些实验室菌株）感染的小鸡喝饮料，不会对它们造成伤害，但确实大大减少了它们肠道内沙门氏菌的数量。现在我们正在申请资金，以便能够研究去除最多沙门氏菌的最佳剂量是多少。蛭弧菌是如何在小鸡体内起作用的，哪些因素是重要的，如果我们使用从鸡体内分离出来的蛭弧菌，这些蛭弧菌在去除沙门氏菌方面比实验室的蛭弧菌更好，而不会伤害鸡，也不会伤害那些可能继续烹饪和食用它们的人。我们将与一个数学模型师合作，对我们收集的所有数据进行计算，计算出当蛭弧菌杀死沙门氏菌时，每只鸡的肠道内发生了什么，并找出这可能如何防止鸟群中的感染。我们的想法是开发蛭弧菌作为治疗人类、动物和鸟类疾病的一种真正的新疗法，这是第一步。

Bdellovibrio are small, human-friendly, predatory bacteria which invade the cells of other pathogenic bacteria (such as ones that give humans food poisoning) and kill them. Bdellovibrio have no activities against human, animal or bird cells but they are naturally good at killing other bacteria. Pathogenic bacteria do not have simple cell surface receptors for Bdellovibrio attachment and invasion and so it is not easy for them to develop resistance to the Bdellovibrio (unlike the situation with conventional antibiotics) Bdellovibrio were discovered in the 1960s and recently we and others have been researching their genes and trying to understand how they may be useful to humans. Previous scientists have published short reports showing that Bdellovibrio has predatory activity against a range of food-borne pathogens, from farm settings, but they usually studied this on food preparation surfaces such as boards or knives, or in foods themselves. No-one has published data on Bdellovibrio treatment of food borne pathogens by Bdellovibrio in farm animals. This leaves Bdellovibrio sitting on the sidelines with much reported potential as an antibacterial agent but no real steps forward in applying it. We wish to do this in our application with human pathogenic Salmonellas including the phage type 4 Salmonella Enteritidis which causes human disease in Europe UK and USA, and in poultry and with bird pathogenic and colonizing strains including Salmonella gallinarum. We have carried out a small pilot project that shows that giving chicks that are colonized with Salmonella, some lab strain Bdellovibrio to drink, does not harm them, but does reduce the numbers of Salmonellas a lot in their intestines. Now we are asking for the funding to be able to study what the best dose of Bdellovibrio is for getting rid of the maximum amount of Salmonellas. How the Bdellovibrio do it exactly inside the chicks and what factors are important, and whether if we use Bdellovibrios we have isolated from inside chickens poultry farms, these ones are better than the lab Bdellovibrio at removing the Salmonellas without harming the chickens, or the people who may go on to cook and eat them. We will work with a mathematical modeller on all the data we collect to calculate what is going on inside each chicken's gut as the Bdellovibrio are killing the Salmonella and to work out how this might prevent infections in flocks of birds. The idea is to develop Bdellovibrio as a real new treatment for human, animal and bird disease and this is the first step.