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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630537
• 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致病机理。抗生素耐药性是世界上最紧迫的公共卫生问题之一，而C。产气荚膜杆菌已成为食源性疾病的最常见细菌原因之一。C.产气荚膜杆菌还在动物中引起多种疾病，例如坏死性肠炎，其可对食用动物生产具有显著的经济影响。我们建立了临床分离株和临床分离株的培养物收集库。产气荚膜梭菌来自不同的动物物种，包括人类。我们是第一个鉴定和鉴定编码获得性杆菌肽耐药的基因的人。产气荚膜杆菌最近，我们已经证明了生物膜形成C。产气荚膜杆菌生物被膜被定义为封闭在自生聚合物基质中的细菌细胞的结构化群落。生物膜的重要特性是它可以增加对抗生素的抗性并促进在环境中的持久性。该建议的指导假设是生物膜有助于致病和抗生素耐药性的C。产气荚膜杆菌，并且抑制其生物膜基质聚合物生物合成将防止生物膜形成。本研究的短期目标是：（i）表征C.产气荚膜梭菌;（ii）鉴定C.本发明的目的在于：（i）使用转录组学方法使用RNA测序鉴定在生物膜形成中表达的基因;（iii）使用靶向诱变方法构建生物膜突变体的集合;（iv）评价生物膜在发病机理和抗生素抗性中的贡献;以及（V）筛选和鉴定生物膜形成的抑制剂。确定了C.产气荚膜杆菌将有助于开发新的疫苗策略或涉及生物膜抑制的新分子。本研究对了解生物膜在念珠菌持续存在、致病机制和耐药性中的作用具有重要意义。产气荚膜杆菌