In Clostridium perfringens, a 5-membered thiolactone peptide acts as an autoinducing peptide (AIPCp) to activate the VirSR two-component signal transduction system, which in turn controls the expression of genes encoding multiple toxins, including α, θ and κ. To develop anti-pathogenic agents against virulent C. perfringens, quorum-quenching peptides were rationally designed based on the structure-activity relationship (SAR) data on AIPCp. Alanine scanning study of AIPCp suggested that Trp3 and Phe4 are involved in receptor binding and activation, respectively. On the basis of the SAR, we designed two quorum-quenching peptides with different modes of action: Z-AIPCp-L2A/T5A (partial agonist) and Z-AIPCp-F4A/T5S (partial antagonist). Both peptides significantly attenuated transcription of θ toxin gene (pfoA) in a virulent strain of C. perfringens with IC50 = 0.32 and 0.72 μM, respectively.
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