title: The resveratrol tetramer (-)-hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.
abstract: Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)-Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.
authors: Umeå Centre for Microbial Research, Laboratories for Infection Medicine Sweden, Department of Chemistry, Umeå University, Umeå, Sweden.
authors: Caroline E
authors: CE
authors: Zetterström
authors: Jenny
authors: J
authors: Hasselgren
authors: Olli
authors: O
authors: Salin
authors: Rohan A
authors: RA
authors: Davis
authors: Ronald J
authors: RJ
authors: Quinn
authors: Charlotta
authors: C
authors: Sundin
authors: Mikael
authors: M
authors: Elofsson
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000187:drug effects*; D015153:Blotting, Western; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D010636:Phenols; D021381:Protein Transport / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects; D015011:Yersinia pseudotuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D010636:Phenols; D013267:Stilbenes; C518233:hopeaphenol; D000077185:Resveratrol