title: Rationale design of quorum-quenching peptides that target the VirSR system of Clostridium perfringens.
abstract: 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 Trp(3) and Phe(4) 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.
authors.affiliation: Laboratory of Microbial Technology, Department of Biochemistry and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Ravindra Pal
authors.initials: RP
authors.lastname: Singh
authors.affiliation: Laboratory of Microbial Technology, Department of Biochemistry and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Okubo
authors.affiliation: Department of Bacteriology, University of Kanazawa, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8203, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ohtani
authors.affiliation: Laboratory of Microbial Technology, Department of Biochemistry and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Keika
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Laboratory of Microbial Technology, Department of Biochemistry and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan Laboratory of Functional Food Design, Department of Functional Metabolic Design, Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomoto
authors.affiliation: Laboratory of Microbial Technology, Department of Biochemistry and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka 812-8581, Japan nakayama@agr.kyushu-u.ac.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D003016:Clostridium perfringens / Q000187:drug effects* / Q000502:physiology*; D004252:DNA Mutational Analysis; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D010455:Peptides; D037521:Virulence Factors
keywords: Clostridium perfringens; quorum sensing; quorum-sensing inhibitor; synthetic AIPCp analogous; toxin gene