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

在不同的动物物种中，有许多非常重要但特征不明确的肠道疾病与产气荚膜梭状芽胞杆菌有关，这种细菌会导致严重甚至致命的疾病。这些疾病的范围从通常致命的疾病，如牛的出血性胃炎和马的伤寒结肠炎，到不太严重的疾病，如猪的新生儿肠炎。由于对产气荚膜原梭菌的作用不确定，因此对这些疾病的诊断和控制也不确定，因此缺乏对这些疾病的特征描述。它还导致抗生素的非靶向使用，从而可能增强抗生素耐药性。产气荚膜荚膜杆菌作为严重肠道疾病的病因，其多样性和进化的关键是一种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。该区域插入到原生质粒中导致交配区域的分化发展，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优势，也使其有能力在不同的动物物种中引起疾病。该研究项目将在三种重要的动物肠道感染（小牛、猪、马）中描述与这些质粒相关的新遗传区域和毒素基因，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。该程序有可能在理解产气荚膜梭菌作为动物疾病的原因方面产生革命性的变化，并可能在人类产气荚膜梭菌相关肠道疾病中具有重要应用。

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.