Plasmids and virulence in animal disease isolates of type A Clostridium perfringens

与产气荚膜梭菌有关的不同动物物种中有许多非常重要但特征不佳的肠道疾病，它们是导致严重和往往致命疾病的原因。这些疾病从常见的致命疾病，如牛的出血性皱胃炎和马的伤寒结肠炎，到不太严重的疾病，如猪的新生肠炎。缺乏这些疾病的特征在于对产气荚膜梭菌作用的不确定性，因此也就是对诊断和控制的不确定性。它还导致无针对性地使用抗生素，从而潜在地增强抗生素耐药性。作为严重肠道疾病的病因，产气荚膜梭菌的多样性和进化的一个关键是被称为质粒的独特的物种限制性遗传结构家族，它可以通过交配在菌株之间移动。将该区域插入到天然质粒中导致交配区的不同发展，并导致后来获得新的毒素和抗生素抗性基因。这为细菌提供了选择性优势，也使其能够适应不同动物物种的疾病。该研究计划将在动物(小牛、猪、马)的三种不同的重要肠道感染中表征与这些质粒相关的新的遗传区和毒素基因，以了解它们是如何参与疾病的，以及如何更好地诊断和控制这些疾病。这项计划有可能使人们对产气荚膜梭菌作为动物致病原因的认识发生革命性的变化，并可能对人类产气荚膜梭菌相关性肠道疾病有重要的应用。

There are a number of very important but not-well-characterized intestinal diseases of different animal species associated with the bacterium Clostridium perfringens, which are responsible for serious and often fatal illness. These range from commonly fatal diseases such as haemorrhagic abomasitis of cattle and typhlocolitis of horses, to less severe diseases such as neonatal enteritis of swine. The lack of characterization of these diseases rests on the uncertainty about the role of C. perfringens, and therefore uncertainties about diagnosis and control. It also leads to non-targeted use of antibiotics and thus potentially enhances antibiotic resistance. A key to the diversity and evolution of C. perfringens as a cause of serious intestinal disease is the unique family of species-restricted genetic structures called plasmids, which can move between strains by mating. The insertion of this region into a native plasmid has led to divergent development of the mating region, and to the later acquisition of new toxin and antibiotic resistance genes. This provides selective advantage to the bacterium and also results in its ability to adapt to cause disease in different animal species. The program of research will characterize the novel genetic regions and toxin genes associated these plasmids in three different important intestinal infections of animals (calves, pigs, horses) to understand how these are involved in disease, and how these diseases can be better diagnosed and controlled. This program has the potential to make a revolutionary change in understanding of C. perfringens as a cause of disease in animals, and may have important application for C. perfringens-associated intestinal diseases in people.