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© Jean-Claude Antoine
Leishmania mexicana amazonensis
Publication : PLoS neglected tropical diseases

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS neglected tropical diseases - 08 Jun 2017

Lamotte S, Späth GF, Rachidi N, Prina E

Link to Pubmed [PMID] – 28594938

PLoS Negl Trop Dis 2017 Jun;11(6):e0005480

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.

https://www.ncbi.nlm.nih.gov/pubmed/28594938