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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=611485
• 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导致食源性疾病的最常见细菌之一。产气荚膜梭菌还会引起多种动物疾病，如坏死性肠炎，这会对食用动物生产产生重大的经济影响。我们已经建立了包括人类在内的不同动物物种的临床和共生产气荚膜梭菌的培养集合。我们首次鉴定和表征了产气荚膜梭菌获得性杆菌素耐药性的编码基因。最近，我们展示了产气荚膜假单胞菌的生物膜形成。生物膜被定义为包裹在自己产生的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药性，并促进环境中的持久性。这一建议的指导假设是，生物膜与产气荚膜杆菌的发病机制和耐药性有关，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)确定产气荚膜杆菌生物膜形成的特征；(Ii)利用RNA测序的转录方法鉴定产气荚膜杆菌生物膜形成过程中涉及的基因；(Iii)利用靶向突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；以及(V)筛选和鉴定生物膜形成的抑制剂。识别产气荚膜梭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生物被膜抑制的新分子。这项工作对于了解生物膜在产气荚膜杆菌的持久性、致病机制和对抗生素的耐药性中的作用具有重要意义。