Silencing Pseudomonas virulence

PhD ceremony: Ms. E. Papaioannou, 13.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertaton: Silencing Pseudomonas virulence

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

Faculty: Mathematics and Natural Sciences

The use of antibiotics in the treatment of bacterial diseases has led to the emergence of antibiotic-resistant “superbugs”. For preventing this emergence of resistant bacteria, alternative treatment methods are required. Evelina Papaiaoannou invented such a method.

By understanding the mechanism by which the Gram-negative opportunistic pathogen Pseudomonas aeruginosa imposes its virulence, potential targets for alternative antimicrobial therapy to the often-fatal infections caused by this pathogen can be identified. Today, we appreciate that P. aeruginosa imposes its virulence via a tightly controlled cell-to-cell communication mechanism referred to as quorum sensing (QS) through diffusible signal molecules referred to as acyl-homoserine lactones (AHL). Interfering with these signal molecules, either by preventing their synthesis and/or accumulation or by prohibiting their binding to their cognate receptor, offers a promising strategy for controlling and eradicating Pseudomonas-related infections.

Prevention of AHL accumulation can be achieved by the degradation of these molecules. Papaiaoannou made clear that there are two groups of enzymes known to degrade AHLs: (1) AHL-lactonases, which hydrolyse the lactone ring and (2) AHL-acylases, which hydrolyse the amide bond between the acyl chain and the homoserine lactone in the AHL molecule, thus generating the corresponding free fatty acid and the homoserine lactone. Papaiaoannou proved P. aeruginosa PAO1 possesses at least three genes encoding for AHL-acylases that are able to degrade the 3-oxo-C12-HSL signal molecule produced by the pathogen itself. These AHL-acylases are thereby able to silence the communication system of this opportunistic pathogen and may therefore serve as potential antimicrobials against Pseudomonas infections.