Proefschrift

Inhibitors and probes targeting PslG

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide, Psl, into smaller fragments.

Auteur

G. Ruijgrok

Datum

12 september 2024

Links

Thesis in Leiden Repository

This decreases the antibiotic resistance of P. Aeruginosa. Interestingly PslG is produced by P. Aeruginosa itself, where it is found on the synthesis gene of Psl. The exact effects of PslG remain partly unknown. Moreover, only hypotheses have been made as to why P. Aeruginosa expresses such an enzyme. Here we have developed a set of activity-based probes based on Psl to discover the mode of action of PslG. Subsequently, a set of inhibitors have been designed based on the Psl motive and the mechanism of action of PslG. PslG was then co-crystallized with the inhibitors in order to study their binding interactions.

• active-based protein profiling (abpp)
• biofilm formation
• glycosylation
• inhibition
• mechanism-based
• pseudomonas aeruginosa
• synthetic carbohydrate chemistry