Using metabolomic approaches to characterize the human pathogen Leishmania in macrophages

Abstract

Leishmania are sandfly-transmitted protozoan parasites that cause a spectrum of diseases ranging from self-healing cutaneous to lethal visceral infections that affect more than 12 million people worldwide. Leishmania alternate between extracellular promastigote stages in the mid-gut of the sandfly and an obligate intracellular amastigote stage that targets macrophages and other monocytes in the mammalian host, residing within the phagolysosome compartment. Each of these stages appear to be well adapted to dealing with a plethora of antimicrobial processes in these diverse host niches, as well as salvaging and utilizing different carbon sources and essential nutrients. Recent studies have highlighted marked differences in the metabolism of these life-cycle stages which appear to be important for transmission and/or persistence and virulence in the mammalian host. This information is crucial for guiding the development of new therapies. In this chapter, we review our current understanding of Leishmania metabolism and what role '-omics’ approaches have played in advancing our understanding. We highlight the role of metabolomic approaches to reveal the mode of action of antileishmanial drugs and to obtain new insights into the activity of metabolic pathways and the physiological state of Leishmania life-cycle stages.