A divergent protein kinase A regulatory subunit essential for morphogenesis of the human pathogen Leishmania.

Parasitic protozoa of the genus Leishmania cycle between the phagolysosome of mammalian macrophages, where they reside as rounded intracellular amastigotes, and the midgut of female sand flies, which they colonize as elongated extracellular promastigotes. Previous studies indicated that protein kinase A (PKA) plays an important role in the initial steps of promastigote differentiation into amastigotes. Here, we describe a novel regulatory subunit of PKA (which we have named PKAR3) that is unique to Leishmania and most (but not all) other Kinetoplastidae.

Macrophage metallothioneins participate in the antileishmanial activity of antimonials.

Host cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of drugs against intracellular pathogen infections are critical for drug efficacy. In this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to the elimination of intracellular upon exposure to pentavalent antimonials (Sb). Primary macrophages from patients with cutaneous leishmaniasis (CL) (n=6) were exposed to infection and Sb, and transcriptomes were generated.

Host-Free Systems for Differentiation of Axenic Leishmania.

This chapter describes, in detail, the method our laboratory developed to differentiate L. donovani promastigotes into amastigotes in a host-free culture. This method is based on previous observations that Leishmania promastigotes can combine two environmental signals, typical to lysosomes, acidic pH (~5.