title: Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium.
abstract: As an important food-borne human pathogen, Salmonella enterica serovar Typhimurium depends on its type III secretion system (T3SS) as a major virulence factor to cause disease all over the world. The T3SS secretes effector proteins to facilitate invasion into host cells. In this study, twenty prenylated flavonoids (1-20) were screened for their anti-T3SS activity, revealing that several analogs exhibited strong inhibitory effects on the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins without affecting the growth of bacteria and the secretion of the flagellar protein FliC. Among the flavonoids 1-20, licoflavonol (20) exhibited a strong inhibitory effect on the secretion of the SPI-1 effector proteins via regulating the transcription of the SicA/InvF genes, and the transportation of the effector protein SipC. In summary, licoflavonol, a novel natural inhibitor of Salmonella T3SS, could be a promising candidate for novel type of anti-virulence drugs.
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China. Electronic address: ahua0966@sdu.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China; State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China. Electronic address: yshen@sdu.edu.cn.
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D012485:Salmonella typhi / Q000187:drug effects / Q000502:physiology*; D000069296:Type III Secretion Systems / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D005419:Flavonoids; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C094577:SicA protein, Salmonella typhimurium; D000069296:Type III Secretion Systems; C090991:invG protein, Salmonella typhimurium; C041477:3-hydroxyflavone
keywords: Licoflavonol; Salmonella enterica serovar Typhimurium; Type three secretion system (T3SS)