Enhancing the copy number of Ldrab6 gene in Leishmania donovani parasites mediates drug resistance through drug - thiol conjugate dependent multidrug resistance protein A (MRPA).

Enhancing the copy number of Ldrab6 gene in Leishmania donovani parasites mediates drug resistance through drug - thiol conjugate dependent multidrug resistance protein A (MRPA). Acta Trop. 2019 Sep 03;:105158 Authors: Chauhan IS, Rao GS, Singh N Abstract Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan Leishmania donovani parasite which may be fatal if left untreated. While drug-sensitive parasites are able to live and multiply within the host macrophages, they develop resistance to drugs used against them for survival and multiplication in the infected patients undergoing routine treatment. Development of new agents devoid of such drug resistance potential is achievable by identifying new drug targets in the parasite. One such target is the key regulator of intracellular vesicular trafficking protein, RabGTPase which belongs to the Ras GTPase superfamily. We recently elucidated whole genome sequence (WGS) of L. donovani (clinical Indian isolate; BHU 1220, GenBank: AVPQ00000000.1) and identified Ldrab6 gene. We now provide experimental evidence for this gene's ability to impart drug-resistant phenotype to wild-type (sensitive) Leishmania upon transfection. trans-Dibenzalacetone (DBA), a synthetic analog of curcumin, was used to determine its antileishmanial activity in wild-type parasites and parasites transfected with Ldrab6 gene. Dose-response study showed that DBA had no effect on transfected parasi...
Source: Acta Tropica - Category: Infectious Diseases Authors: Tags: Acta Trop Source Type: research