Functional characterization of the Pneumocystis jirovecii potential drug targets dhfs and abz2 involved in folate biosynthesis.

Détails

Ressource 1Télécharger: BIB_CC1DFBDCA1FE.P001.pdf (3233.36 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_CC1DFBDCA1FE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Functional characterization of the Pneumocystis jirovecii potential drug targets dhfs and abz2 involved in folate biosynthesis.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Luraschi A., Cissé O.H., Monod M., Pagni M., Hauser P.M.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
59
Numéro
5
Pages
2560-2566
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Pneumocystis species are fungal parasites colonizing mammal lungs with strict host specificity. Pneumocystis jirovecii is the human-specific species and can turn into an opportunistic pathogen causing severe pneumonia in immunocompromised individuals. This disease is currently the second most frequent life-threatening invasive fungal infection worldwide. The most efficient drug, cotrimoxazole, presents serious side effects, and resistance to this drug is emerging. The search for new targets for the development of new drugs is thus of utmost importance. The recent release of the P. jirovecii genome sequence opens a new era for this task. It can now be carried out on the actual targets to be inhibited instead of on those of the relatively distant model Pneumocystis carinii, the species infecting rats. We focused on the folic acid biosynthesis pathway because (i) it is widely used for efficient therapeutic intervention, and (ii) it involves several enzymes that are essential for the pathogen and have no human counterparts. In this study, we report the identification of two such potential targets within the genome of P. jirovecii, the dihydrofolate synthase (dhfs) and the aminodeoxychorismate lyase (abz2). The function of these enzymes was demonstrated by the rescue of the null allele of the orthologous gene of Saccharomyces cerevisiae.
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/06/2015 15:14
Dernière modification de la notice
09/05/2019 1:19
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