The quorum-quenching acylase PvdQ. Biological role & directed evolution

PhD ceremony: Ms. G. Koch, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: The quorum-quenching acylase PvdQ. Biological role & directed evolution

Promotor(s): prof. W.J. Quax

Faculty: Mathematics and Natural Sciences

Quorum-quenching enzymes represent a promising strategy in the fight against infections with Gram-negative bacteria. These microbes generally use small chemical molecules, N-acyl homoserine lactones (AHLs), to coordinate gene expression in a cell-density dependent manner. This phenomenon, called quorum sensing, is a conserved regulatory mechanism associated with the expression of virulence traits. Particular attention is given here to the quorum-quenching acylase PvdQ which can be found in all fluorescent Pseudomonas spp. Despite its involvement in AHL degradation, the primary function of PvdQ seems to be its involvement in the biosynthesis of the major siderophore pyoverdine, a potent iron-scavenging molecule essential for bacterial survival. This thesis highlights in detail the role of this acylase under physiological conditions, but also further explores its potential as a promising antimicrobial by interfering with AHL-dependent quorum sensing.