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

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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.