Study on the contribution of biofilm in the pathogenesis and in the resistance to antibiotics in Clostridium perfringens.

生物膜在产气荚膜梭菌发病机制和抗生素耐药性中的贡献研究。

• 批准号: RGPIN-2014-05183
• 负责人: Archambault, Marie
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567001
• 关键词: Study; contribution; biofilm; pathogenesis; resistance

This research program has the long-term objective of a better understanding of the resistance to antibiotics and the pathogenesis of Clostridium perfringens. Antibiotic resistance is one of the world's most pressing public health issues while C. perfringens has become one of the most common bacterial causes of food-borne illness. C. perfringens causes also a wide variety of diseases in animals such as necrotic enteritis which can have a significant economic impact on food animal production. We have built a culture collection of clinical and commensal isolates of C. perfringens from different animal species including humans. We were the first to identify and characterize genes encoding for acquired bacitracin resistance in C. perfringens. More recently, we have demonstrated biofilm formation in C. perfringens. Biofilm has been defined as a structured community of bacterial cells enclosed in a self-produced polymeric matrix. Important properties of biofilm are that it can increase resistance to antibiotics and promote persistence in the environment. The guiding hypothesis of this proposal is that biofilms contribute to the pathogenesis and the antibiotic resistance of C. perfringens and that inhibition of its biofilm matrix polymers biosynthesis will prevent biofilm formation. The short-term objectives of this research are: (i) to characterize biofilm formation of C. perfringens; (ii) to identify genes involved during C. perfringens biofilm formation using a transcriptomic approach using RNA sequencing to identify genes that are expressed in biofilm formation; (iii) to construct a collection of biofilm mutants using targetron-mutagenesis approach; (iv) to evaluate the contribution of biofilm in pathogenesis and antibiotic resistance; and (v) to screen and identify inhibitors of biofilm formation. Identifying key genes and regulatory genetic systems in C. perfringens will contribute to the development of new vaccine strategies or novel molecules involved in the inhibition of biofilms. This work is important to understand the contribution of biofilm to the persistence, the pathogenesis, and in the resistance to antibiotics of C. perfringens.

这项研究计划的长期目标是更好地了解产气荚膜梭菌对抗生素的耐药性和发病机制。抗生素耐药性是世界上最紧迫的公共卫生问题之一，而产气荚膜梭菌已成为食源性疾病最常见的细菌原因之一。产气荚膜梭菌还会在动物中引起各种各样的疾病，如坏死性肠炎，对食用动物的生产产生重大的经济影响。我们从包括人类在内的不同动物物种中建立了临床和共生分离的产气荚膜荚膜杆菌培养集。我们首次鉴定并鉴定了产气荚膜荚膜杆菌获得性杆菌肽抗性的编码基因。最近，我们已经证明了产气荚膜梭菌的生物膜形成。生物膜被定义为一种结构群落的细菌细胞封闭在一个自产的聚合物基质。生物膜的重要特性是它可以增加对抗生素的耐药性并促进在环境中的持久性。本研究的指导假设是生物膜参与了产气荚膜梭菌的发病机制和抗生素耐药性，抑制其生物膜基质聚合物的生物合成将阻止生物膜的形成。本研究的短期目标是：(i)表征产气荚膜梭菌的生物膜形成；（ii）利用转录组学方法鉴定产气荚膜梭菌生物膜形成过程中涉及的基因，利用RNA测序方法鉴定生物膜形成过程中表达的基因；（iii）利用靶子诱变方法构建生物膜突变体集合；（iv）评价生物膜在发病机制和抗生素耐药性中的作用；(5)筛选和鉴定生物膜形成抑制剂。确定产气荚膜荚膜杆菌的关键基因和调控遗传系统将有助于开发新的疫苗策略或参与抑制生物膜的新分子。这项工作对了解产气荚膜荚膜菌的持久性、发病机制以及对抗生素的耐药性具有重要意义。