The use of quorum quenching enzymes and quorum sensing inhibitors to combat pseudomonas aeruginosa and acinetobacter baumannii biofilm-related infections

Yunhui Zhang
Faculteit Farmaceutische Wetenschappen
Vakgroep Farmaceutische Analyse
Master, Ocean University of China, 2014
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Vertaling titel
Het gebruik van enzymen met quorum quenching activiteit en quorum sensing inhibitoren om biofilm-geassocieerde infecties met Pseudomonas aeruginosa en Acinetobacter baumannii te bestrijden
Prof. dr., Tom Coenye, UGent-Farmaceutische Analyse
Prof. dr., Serge Van Calenbergh, UGent-Geneesmiddelenleer - Prof. dr., Kevin Braeckmans, UGent-Geneesmiddelenleer - Dr., Aurélie Crabbé, UGent-Farmaceutische Analyse - Dr., Heleen Van Acker, UGent-Farmaceutische Analyse - Prof. dr., Tom Defoirdt, UGent-Fac. Bioingenieurswetenschappen - Prof. dr., Hans Steenackers, KULeuven

Korte beschrijving

Quorum sensing (QS) systems of many clinical relevant pathogens are involved in regulating various processes associated with virulence. This allows bacteria to achieve a coordinated attack on the host at a high population density and overcome the host defense successfully. Therefore, QS inhibition either by quorum quenching (QQ) enzymes or QS inhibitors (QSIs) has been considered as an attractive therapeutic strategy to treat infections caused by pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii. In this dissertation, we explored the effects of typical QQ enzyme and QSIs on P. aeruginosa and A. baumannii, aiming to identify promising QS inhibition agents to reduce virulence and biofilm formation of P. aeruginosa and A. baumannii. In this dissertation, we first evaluated the anti-biofilm activity of the QQ enzyme MomL against P. aeruginosa and A. baumannii, and further investigated the effect of MomL under more complex conditions such as in dual-species biofilm and in a wound model system. The effect of MomL on virulence of A. baumannii was also tested in the Caenorhabditis elegans infection model. Secondly, the effects of a plant-derived QSI, coumarin, on the production of virulence factors and biofilm formation in several P. aeruginosa wound isolates were investigated. We also aimed to test the potential use of coumarin to increase the survival of Lucilia sericata when challenged with P. aeruginosa in the context of wound debridement therapy. In addition, transcriptome analysis was performed to reveal how coumarin affected QS and virulence in P. aeruginosa. Finally, we aimed to expand the knowledge about QSIs which were effective against A. baumannii. The effects of several known QSIs on A. baumannii motility and biofilm formation were tested. The most promising QSIs against A. baumannii were further evaluated in a Galleria mellonella infection model.


Dinsdag 26 juni 2018, 18:00
Auditorium 2, Ottergemsesteenweg 460, 9000 Gent