Leishmania major LmACR2 Is a Pentavalent Antimony Reductase That Confers Sensitivity to the Drug Pentostam

Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug pentostam.

Arsenicals and antimonials are first line drugs for the treatment of trypanosomal and leishmanial diseases. To create the active form of the drug, Sb(V) must be reduced to Sb(III). Because arsenic and antimony are related metalloids, and arsenical resistant Leishmania strains are frequently cross-resistant to antimonials, we considered the possibility that Sb(V) is reduced by a leishmanial As(V...

Pentostam activation and uptake in Leishmania major: Role of the Sb(V) reductase LmAcr2 and the aquaglyceroporin LmAqp1

A novel marker, ARM58, confers antimony resistance to Leishmania spp.☆

Protozoa of the Leishmania genus cause a variety of disease forms that rank at the top of the list of neglected tropical diseases. Anti-leishmanial drugs based on pentavalent antimony have been the mainstay of therapy for over 60 years and resistance against them is increasingly encountered in the field. The biochemical basis for this is poorly understood and likely diverse. No stringent correl...

A new ABC half-transporter in Leishmania major is involved in resistance to antimony.

The characterization of ABCI4, a new intracellular ATP-binding cassette (ABC) half-transporter in Leishmania major, is described. We show that ABCI4 is involved in heavy metal export, thereby conferring resistance to Pentostam, to Sb(III), and to As(III) and Cd(II). Parasites overexpressing ABCI4 showed a lower mitochondrial toxic effect of antimony by decreasing reactive oxygen species product...

Susceptibility of clinical strains of Leishmania to pentavalent antimony and miltefosine: challenges and opportunities

Introduction Passive case detection and treatment constitute the principal and often the sole measure of control for dermal leishmaniasis in Central and South America yet pentavalent antimonials, the first line therapy, are often ineffective. Treatment failure is frequent and concerning in the management of cutaneous leishmaniasis in South America. Overall non-response is of the order of 24% ba...