The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue PLoS Neglected Tropical Diseases Année : 2017

The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

Résumé

The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.
Fichier principal
Vignette du fichier
journal.pntd.0005480.pdf (1.39 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

pasteur-01570238 , version 1 (28-07-2017)

Licence

Paternité

Identifiants

Citer

Suzanne Lamotte, Gerald F Späth, Najma Rachidi, Eric Prina. The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery. PLoS Neglected Tropical Diseases, 2017, 11 (6), pp.e0005480. ⟨10.1371/journal.pntd.0005480⟩. ⟨pasteur-01570238⟩

Collections

INSERM PASTEUR ANR
156 Consultations
244 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More