title: Specific quorum sensing-disrupting activity (A QSI) of thiophenones and their therapeutic potential.
abstract: Disease caused by antibiotic resistant pathogens is becoming a serious problem, both in human and veterinary medicine. The inhibition of quorum sensing, bacterial cell-to-cell communication, is a promising alternative strategy to control disease. In this study, we determined the quorum sensing-disrupting activity of 20 thiophenones towards the quorum sensing model bacterium V. harveyi. In order to exclude false positives, we propose a new parameter (AQSI) to describe specific quorum sensing activity. AQSI is defined as the ratio between inhibition of quorum sensing-regulated activity in a reporter strain and inhibition of the same activity when it is independent of quorum sensing. Calculation of AQSI allowed to exclude five false positives, whereas the six most active thiophenones (TF203, TF307, TF319, TF339, TF342 and TF403) inhibited quorum sensing at 0.25 μM, with AQSI higher than 10. Further, we determined the protective effect and toxicity of the thiophenones in a highly controlled gnotobiotic model system with brine shrimp larvae. There was a strong positive correlation between the specific quorum sensing-disrupting activity of the thiophenones and the protection of brine shrimp larvae against pathogenic V. harveyi. Four of the most active quorum sensing-disrupting thiophenones (TF 203, TF319, TF339 and TF342) were considered to be promising since they have a therapeutic potential of at least 10.
authors.affiliation: Laboratory of Aquaculture &Artemia Reference Center, Ghent University, Belgium.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Oral Microbiology, University of Oslo, Norway.
authors.forename: Anne Aamdal
authors.initials: AA
authors.lastname: Scheie
authors.affiliation: Department of Chemistry, University of Oslo, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Benneche
authors.affiliation: Laboratory of Aquaculture &Artemia Reference Center, Ghent University, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Defoirdt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001156:Artemia / Q000187:drug effects / Q000382:microbiology; D001419:Bacteria / Q000187:drug effects; D007814:Larva; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010636:Phenols; D013438:Sulfhydryl Compounds; C042983:thiophenol