TY - JOUR
T1 - Exploitation of auxotrophies and metabolic defects in Toxoplasma as therapeutic approaches
AU - Coppens, Isabelle
N1 - Funding Information:
I thank all former and current members of my laboratory for their scientific contributions highlighted in this review. I am also grateful to Julia Romano for editorial assistance and excellent scientific comments of the manuscript. Finally I acknowledge grants from the US National Institutes of Health and the American Heart Association .
PY - 2014/2
Y1 - 2014/2
N2 - 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, emphasising 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.
AB - 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, emphasising 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.
KW - Apicomplexan parasites
KW - Auxotrophy
KW - Host cell adaptations
KW - Inhibitors of transporters
KW - Intracellular parasitism
KW - Mechanisms of nutrient diversion
KW - Salvage pathways
KW - Toxoplasma
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U2 - 10.1016/j.ijpara.2013.09.003
DO - 10.1016/j.ijpara.2013.09.003
M3 - Review article
C2 - 24184910
AN - SCOPUS:84892499849
VL - 44
SP - 109
EP - 120
JO - International Journal for Parasitology
JF - International Journal for Parasitology
SN - 0020-7519
IS - 2
ER -