Biosynthesis and catabolism of mannitol is developmentally regulated in the protozoan parasite Eimeria tenella

The mannitol cycle is a metabolic branch of the glycolytic pathway found in Eimeria tenella. In this paper, we describe the biosynthesis and consumpti on of mannitol during parasite development. Low micromolar levels of mannit ol were detected in all of the asexual stages and mannitol production incre ased sharply during the sexual phase of the life cycle. Unsporulated oocyst s had high mannitol content (300 mM or 25% of the oocyst mass). Mannitol-1- phosphate dehydrogenase (M1PDH), the first committed step of the mannitol c ycle, was also elevated in sexual stages and this coincides with mannitol l evels. Approximately 90% of the mannitol present in unsporulated oocysts wa s consumed in the first 15 hr of sporulation, and levels continued to drop until the sporulation process was complete at similar to 35 hr. Thus, manni tol appears to be the "fuel" for sporulation during the vegetative stage of the parasite life cycle. Evaluation of oocyst extracts from 6 additional E imeria species for mannitol content and the presence of M1PDH indicated tha t the mannitol cycle was broadly present in this genus. This finding combin ed with the lack of mannitol metabolism in higher eukaryotes makes this pat hway an attractive chemotherapeutic target.