Contribution to the understanding of Pseudomonas aeruginosa virulence in search of innovative therapeutic approaches : focus on the type III secretion system
(2017)
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- Abstract
- The treatment of bacterial infections is becoming more challenging, with increasing rates of antibiotic resistance not only to currently used antipseudomonal drugs but also to recently developed compounds. Alternative treatment options are thus needed that are less prone to select resistance mechanisms. We focused our work on the type III secretion system (T3SS), a key virulence factor associated with poor clinical outcome and high morbidity in P. aeruginosa acute infections. In this context, the PhD thesis aimed at understanding and modulating the interaction between P. aeruginosa and host cells mediated by the type III secretion system. We showed that, beyond the directs effects of T3SS toxins, inflammasome activation is a crucial mechanism involved in T3SS cytotoxic effects. In a murine model of acute pneumonia, T3SS inhibitors caused a decrease in inflammatory lesions, bacterial invasion and dissemination and an increased in bacterial clearance Targeting T3SS allows not only attenuating toxin effects but also modulating favorably the host inflammatory response, whatever the resistance profile of the P.aeruginosa strains. The results of this research are paving the way for new therapeutic approaches against P. aeruginosa.
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Citations
Anantharajah, A. (2017). Contribution to the understanding of Pseudomonas aeruginosa virulence in search of innovative therapeutic approaches : focus on the type III secretion system. https://hdl.handle.net/2078.5/91494