Contribution of host lipids to Toxoplasma pathogenesis

Abstract

As an actively dividing organism, the intracellular parasite Toxoplasma gondii must adjust the size and composition of its membranes in order to accommodate changes due to housekeeping activities, to commit division and in fine to produce new viable progenies. Lipid inventory of T. gondii reveals that the biological membranes of this parasite are composed of a complex mixture of neutral and polar lipids. After examination of the origin of T. gondii membrane lipids, three categories of lipids can be described: (i) lipids scavenged by T. gondii from the host cell; (ii) lipids synthesized in large amounts by the parasite, independently from its host cell; and (iii) lipids produced de novo by the parasite, but whose synthesis does not come close to satisfying the entire parasite's needs. These latter must be adeptly acquired from the host environment. To this end, T. gondii diverts a large variety of lipid precursors from host cytoplasm and efficiently manufacture them into complex lipids. This rather remarkable reliance on host lipid resources for parasite survival opens new avenues to restrict parasite growth. Indeed, parasite starvation can be induced upon deprivation from essential host lipids. Lipid analogues with anti-proliferative properties are voraciously taken up by the parasites, which results in parasite membrane defects, and ultimately death.