Int J Parasitol. 2013 Oct 31. pii: S0020-7519(13)00248-8. doi: 10.1016/j.ijpara.2013.09.003. [Epub ahead of print]

Exploitation of auxotrophies and metabolic defects in Toxoplasma as therapeutic approaches

Coppens I.

Source

Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. Electronic address: icoppens@jhsph.edu.

Abstract

Like any obligate intracellular pathogen, the parasite Toxoplasma gondii has lost its capacity for living independently of another organism. Toxoplasma lacks many genes that encode for entire metabolic pathways and has, in return, expanded genes that promote nutrient scavenging to meet its basic metabolic requirements. Although sequestrated in a parasitophorous vacuole and thus insulated from the nutrient-rich host cytosol and organelles by a membrane, T. gondii has evolved efficient strategies to acquire essential metabolites from mammalian cells. This review explores the natural auxotrophies and nutrient scavenging activities of the parasite, emphasizing unique transport systems and salvage pathways. We describe the mechanisms deployed by Toxoplasma to modify its parasitophorous vacuole to gain access to host cytosolic molecules and to hijack host organelles to retrieve their nutrient content. From a therapeutic perspective, we survey the different possibilities to starve T. gondii by nutrient depletion or disruption of salvage pathways.
Copyright © 2013. Published by Elsevier Ltd.

KEYWORDS:

Apicomplexan parasites, Auxotrophy, Host cell adaptations, Inhibitors of transporters, Intracellular parasitism, Mechanisms of nutrient diversion, Salvage pathways, Toxoplasma

PMID:

24184910

[PubMed - as supplied by publisher]