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New insights into the molecular function of PqsE: providing tools to inhibit the virulence of Pseudomonas aeruginosa

Folch, Benjamin; Déziel, Éric ORCID logoORCID: https://orcid.org/0000-0002-4609-0115 et Doucet, Nicolas ORCID logoORCID: https://orcid.org/0000-0002-1952-9380 (2012). New insights into the molecular function of PqsE: providing tools to inhibit the virulence of Pseudomonas aeruginosa In: 26th Annual Symposium of the Protein-Society, August 05-08, 2012, San Diego, CA.

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Résumé


Pseudomonas aeruginosa is a prevalent opportunistic human pathogen. Individuals who are immunocompromised are especially susceptible to infections by this bacterium, such as cancer and AIDS patients. Additionally, P. aeruginosa is the principal bacterial agent responsible for persistent drug refractile lung infections, sepsis in burn patients, and morbidity and mortality among individuals suffering from cystic fibrosis. It is also a major nosocomial pathogen responsible for many hospital outbreaks and is notorious for its high resistance to antibiotic treatments. P. aeruginosa is known to establish a bacterial cell-to-cell communication named quorum sensing to resist host immune system, leading to full-fledged virulence. The enzyme PqsE is essential for the regulation of quorum sensing and the full virulence of this bacterial species. The enzyme regulates the synthesis of pyocyanin, a toxic compound only produced by P. aeruginosa. As a result, this enzyme is an important drug target showing considerable promise for the design of new inhibitors directed against this opportunistic human pathogen. Based on its structural investigation, we present preliminary enzyme characterization and mutagenesis experiments aimed at altering the biological function of PqsE, allowing the characterization of key amino acid positions involved in the molecular function of the enzyme. This functional mapping will be exploited for designing potential inhibitors through a computational method using a large set of small pharmaceutical compounds. The positive hits will be tested on the purified enzyme to evaluate their potency and to better characterize the role and molecular function played by PqsE in P. aeruginosa. This research should provide new insights and means to counter bacterial infections.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique 250 Protein Science 21(suppl.1):152-153
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 janv. 2024 14:59
Dernière modification: 28 janv. 2024 14:59
URI: https://espace.inrs.ca/id/eprint/14122

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