Faculty Opinions recommendation of Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction.

AbstractMany eukaryotic microbes have complex lifecycles that include both sexual and asexual phases with strict species-specificity. While the asexual cycle of the protistan parasite Toxoplasma gondii can occur in any warm-blooded mammal, the sexual cycle is restricted to the feline intestine1. The molecular determinants that identify cats as the definitive host for T. gondii are unknown. Here, we defined the mechanism of species specificity for T. gondii sexual development and break the species barrier to allow the sexual cycle to occur in mice. We determined that T. gondii sexual development occurs when cultured feline intestinal epithelial cells are supplemented with linoleic acid. Felines are the only mammals that lack delta-6-desaturase activity in their intestines, which is required for linoleic acid metabolism, resulting in systemic excess of linoleic acid2, 3. We found that inhibition of murine delta-6-desaturase and supplementation of their diet with linoleic acid allowed T. gondii sexual development in mice. This mechanism of species specificity is the first defined for a parasite sexual cycle. This work highlights how host diet and metabolism shape coevolution with microbes. The key to unlocking the species boundaries for other eukaryotic microbes may also rely on the lipid composition of their environments as we see increasing evidence for the importance of host lipid metabolism during parasitic lifecycles4, 5. Pregnant women are advised against handling cat litter as maternal infection with T. gondii can be transmitted to the fetus with potentially lethal outcomes. Knowing the molecular components that create a conducive environment for T. gondii sexual reproduction will allow for development of therapeutics that prevent shedding of T. gondii parasites. Finally, given the current reliance on companion animals to study T. gondii sexual development, this work will allow the T. gondii field to use of alternative models in future studies.

Download Full-text

Reduced delta-6 desaturase activity partially protects against high-fat diet-induced impairment in whole-body glucose tolerance

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2019.02.005 ◽

2019 ◽

Vol 67 ◽

pp. 173-181 ◽

Cited By ~ 3

Author(s):

Barbora Hucik ◽

Ousseynou Sarr ◽

Manabu T. Nakamura ◽

David J. Dyck ◽

David M. Mutch

Keyword(s):

Glucose Tolerance ◽

High Fat Diet ◽

Desaturase Activity ◽

Whole Body ◽

High Fat ◽

Delta 6 Desaturase

Download Full-text

Alternative route for the biosynthesis of polyunsaturated fatty acids in K562 cells

Biochemical Journal ◽

10.1042/bj2910841 ◽

1993 ◽

Vol 291 (3) ◽

pp. 841-845 ◽

Cited By ~ 24

Author(s):

J Naval ◽

M J Martínez-Lorenzo ◽

I Marzo ◽

P Desportes ◽

A Piñeiro

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Desaturase Activity ◽

Alternative Pathway ◽

K562 Cells ◽

Chain Elongation ◽

Pufa Biosynthesis ◽

Delta 5 Desaturase ◽

Delta 9 Desaturase ◽

Delta 6 Desaturase

K562 human leukaemia cells lack a significant delta 6-desaturase activity. However, they synthesize long-chain polyunsaturated fatty acids (PUFA) from linoleic (C18:2(9,12)) and linolenic (C18:3(9,12,15)) acids, by reactions involving a C2 chain elongation followed by a delta 5-desaturation step and, to some extent, a further elongation. The main products formed were separated by argentation t.l.c. and identified by g.l.c. as the uncommon fatty acids C20:3(5,11,14) and C20:4(5,11,14,17) respectively. These acids were also produced when cells were supplemented with C20:2(11,14) or C20:3(11,14,17) respectively. The presence of a delta 5-desaturase was further confirmed by using its corresponding normal substrates, C20:3(8,11,14) and C20:4(8,11,14,17), which led to C20:4(5,8,11,14) and C20:5(5,8,11,14,17) respectively. On the other hand, a high delta 9-desaturase activity, but no significant delta 4-desaturase activity, were detected in K562 cells. These results indicate the existence of an alternative pathway, involving delta 5-desaturase, which is the only route for PUFA biosynthesis in K562 cells. This pathway may be relevant for the biosynthesis of PUFA in cells lacking delta 6-desaturase activity.

Download Full-text