Chapter 19: The Macrophage–Parasite Interface as a Chemotherapeutic Target in Leishmaniasis

Parasites of the genus Leishmania are intravacuolar pathogens that create compartments within their mammalian hosts where they can live, replicate and manipulate host immune responses. To generate these parasitophorous vacuoles, Leishmania diverts the default phagolysosomal biogenesis process, in part through the action of virulence factors on the host cell membrane fusion machinery. Components of this machinery essential to the biogenesis, maintenance and function of parasitophorous vacuoles may constitute attractive targets for the design of compounds that will disrupt the integrity of the Leishmania intracellular niche and interfere with parasite replication. Targeting components of the fusion machinery thus represents a promising avenue for the discovery of anti-leishmanial compounds that may not be plagued with problems associated with the development of resistance.