LotaV3, Main, Exploration, bibRecord, 000014

Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

Identifieur interne : 000014 ( Main/Exploration ); précédent : 000013; suivant : 000015

Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

Auteurs : Qian Yang [Belgique] ; Anne Aamdal Scheie [Norvège] ; Tore Benneche [Norvège] ; Tom Defoirdt [Belgique]

Source :

Scientific Reports [ 2045-2322 ] ; 2015.

RBID : PMC:4673447

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 (A_QSI) to describe specific quorum sensing activity. A_QSI 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 A_QSI 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 A_QSI 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673447

DOI: 10.1038/srep18033
PubMed: 26647822
PubMed Central: 4673447

Affiliations:

Belgique, Norvège

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 In order to exclude false positives, we propose a new parameter (A<sub>QSI</sub>
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 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 A<sub>QSI</sub>
 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 A<sub>QSI</sub>
 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 <italic>V. harveyi</italic>
. 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.</p>
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Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

Specific quorum sensing-disrupting activity (AQSI) of thiophenones and their therapeutic potential

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