Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani

Publication date: Available online 21 August 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): M. Shamim Hasan Zahid, Monica M. Johnson, Robert J. Tokarski, Abhay R. Satoskar, James R. Fuchs, Eric M. Bachelder, Kristy M. AinslieAbstractVisceral leishmaniasis (VL) is associated with treatment complications due to the continued growth of resistant parasites toward currently available pathogen-directed therapeutics. To limit the emergence and combat resistant parasites there is a need to develop new anti-leishmanial drugs and alternative treatment approaches, such as host-directed therapeutics (HDTs). Discovery of new anti-leishmanial drugs including HDTs requires suitable in vitro assay systems. Herein, we modified and evaluated a series of resazurin assays against different life-stages of the VL causing parasite, Leishmania donovani to identify novel HDTs. We further analyzed the synergy of combinatorial interactions between traditionally used pathogen-directed drugs and HDTs for clearance of intracellular L. donovani. The inhibitory concentration at 50% (IC50) of the five evaluated therapies [amphotericin B (AMB), miltefosine, paromomycin, DNER-4, and AR-12 (OSU-03012)] was determined against promastigotes, extracellular amastigotes, and intracellular amastigotes of L. donovani via a resazurin-based assay and compared to image-based microscopy. Using the resazurin-based assay, all evaluated therapies showed reproducible anti-leishmanial a...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research