Assessing the evolutionary robustness of anti-biofilm combination therapy.

Promovendus/a
Bové, Mona
Faculteit
Faculteit Farmaceutische Wetenschappen
Vakgroep
Vakgroep Farmaceutische Analyse
Curriculum
Master of science in drug development, Faculty of pharmaceutical sciences, Ghent University, 2016–2018 Bachelor in pharmaceutical sciences, Faculty of pharmaceutical sciences, Ghent University, 2013–2016 Modern languages and science, Sint-Gertrudisch College, Wetteren, 2007–2013
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Engels
Vertaling titel
Evaluatie van de evolutionaire robuustheid van anti-biofilm combinatietherapieën.
Promotor(en)
Prof. dr. Tom Coenye, UGent-Farmaceutische Analyse
Examencommissie
Prof. dr. Aurélie Crabbé, UGent-Farmaceutische Analyse - Prof. dr. Koen Raemdonck, UGent-Geneesmiddelenleer - Prof. Akos Kovacs, Technical University of Denmark - Prof. Charles Van der Henst, VIB-VUB Group leader, MRDD Group - Dr. Bram Van den Bergh, KULeuven - Dr. Charlotte Peeters, UGent-Faculteit Wetenschappen

Korte beschrijving

Besides the well-known problems associated with antibiotic resistance, treatment of bacterial infections is hampered by the fact that bacteria often reside in biofilms. One of the typical properties of biofilm cells is reduced susceptibility to antimicrobial agents, due to lack of penetration of antibiotics, and biofilm-specific protective stress responses. In addition, specific phenotypes with low metabolic activity are induced in biofilms, likely providing an additional mechanism of tolerance. A strategy to increase the antibacterial activity of antibiotics is the use of potentiators. These are compounds that have no antimicrobial activity on their own, but increase the antimicrobial effect of conventional antibiotics in combination therapy. Because potentiators in contrary to antibiotics, do not directly kill pathogens, they are thought to exert less selective pressure on bacteria, and would consequently result in less development of resistance. The aim of this dissertation was to evaluate if combinations of potentiators and antibiotics are ‘evolution-proof’ (i.e., if potentiators would slow down or prevent the development of antibiotic resistance). To this end, two Gram-negative pathogens, Pseudomonas aeruginosa and Burkholderia cenocepacia, that are known to cause difficult to treat, biofilm-associated infections, were experimentally evolved in presence of a combination therapy. To make the experimental results more relevant for the in vivo situation, P. aeruginosa which is a major pathogen in cystic fibrosis, was evolved in a synthetic medium that mimics the environment of the cystic fibrosis lung, and B. cenocepacia was evolved in a non-vertebrate in vivo host. The experiments in this dissertation show that potentiators are able to increase the antimicrobial effect of antibiotics against biofilms and in in vivo models. However, resistance against potentiators can develop, indicating that combination therapies are not by definition ‘evolution-proof’.

Praktisch

Datum
Maandag 19 september 2022, 17:00
Locatie
Faculteit Farmaceutische Wetenschappen - Auditorium B - Andreas Vesalius, Ottergemsesteenweg 460, 9000 Gent