Combating gram-negative-infectious diseases. Controlling virulence factors through quorum quenching acylases of Pseudomonas aeruginosa

PhD ceremony: Ms. M. Wahjudi, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Combating gram-negative-infectious diseases. Controlling virulence factors through quorum quenching acylases of Pseudomonas aeruginosa

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

Faculty: Mathematics and Natural Sciences

Infectious diseases cause a serious problem worldwide. The antibiotic resistance of Gram-negative strains has increased over the last decades. The emergence is so faster than the development of new antibiotics to address those that it is important to find an alternative treatment for the anti-infective against Gram-negative pathogens. Most of the Gram-negative bacteria, including Pseudomonas aeruginosa, have the ability of accommodating a variety of social behaviours, including acyl-homoserine-lactones quorum sensing (AHLs-QS) system. The pathogenicity of P. aeruginosa has been shown to be regulated by the AHLs-QS system. Prevention of the AHLs-mediated QS, called as quorum quenching (QQ), may be useful to stop the modulated-virulence products and will lead to increasing the susceptibility of the pathogens to normal host immune systems.

The alternative presented by Mariana Wahjudi in her thesis deals with bacterial pathogens and circumvention of drugs resistance by disturbing the pathways mediating the virulence without affecting the bacterial survival, growth, or the host’s metabolism. The function of P. aeruginosa AHL-acylases as QQ acylases was studied by her in controlling the virulence factors of P. aeruginosa in in vitro study and in in vivo C. elegans model. In conclusion, she can states that both PvdQ and HacB, the Ntn-hydrolase proteins from P. aeruginosa PAO1, function as quorum quenching AHL-acylases which might be strong candidates for antibacterial therapy against Pseudomonas infections. Wahjudi also demonstrated that the spray-freeze-dried-PvdQ trehalose and inulin based formulations are suitable for pulmonary delivery.