Pre-adaptation of Leishmania promastigotes to intracellular life: ensuring a successful infection

Leishmaniasis is a group of diseases with diverse phenotype from self-healing cutaneous lesions to fatal visceral infections. The complex life-cycle of the parasite Leishmania in its vector and host as well as the vector and host characteristics determine the severity of infection. Leishmania has evolved several strategies to survive as extracellular promastigotes in the sandfly vector and successfully transform to amastigotes sensing an increase in temperature and acidic pH inside the macrophages. In this review we have discussed the physiological and biochemical changes in promastigotes which make them infective and how these infection ready parasites respond to intramacrophagic stress. We have summed up the changes in expression of structural proteins, virulence factors (including species-specific virulence factors), and stress related proteins when the parasites convert to metacyclic promastigotes and then from metacyclics to amastigotes, and how these pathways have been targeted for therapy. The trends in global gene expression of Leishmania under various conditions and at various life-stages using modern molecular biology approaches such as genomics, transcriptomics, proteomics and metabolomics have been discussed in conjunction with the theory of pre-adaptation of the parasites for life inside macrophages