The mannitol cycle in Eimeria

Abstract

A metabolic pathway known as the mannitol cycle has been identified in Eimerian parasites. The pathway is a shunt off of the glycolytic pathway at fructose-6-phosphate (F6P). Two enzymes convert F6P to mannitol and two other enzymes are responsible for converting mannitol back to F6P when it is utilized. Although the pathway is present in various stages of the parasite the most apparent role of this pathway is in the sexual portion of the life cycle, particularly in the formation of oocysts. Extremely high concentrations of mannitol, approaching 0.3 M, are present in unsporulated oocysts. Mannitol functions as the endogenous energy source for oocysts to sporulate in the environment outside of the host. An inhibitory protein which inactivates the first enzyme of the mannitol cycle has been isolated from an oocyst derived inhibited enzyme complex and is believed to prevent the futile cycling of F6P during the maturation of oocysts. Evidence of the vital role of mannitol in the development and maturation of Eimeria tenella oocysts has been facilitated through the use of the drug Nitrophenide™, a known anticoccidial which has now been found to be an inhibitor of one of the enzymes responsible for the biosynthesis of mannitol in the parasite. This compound prevents the formation of oocysts and at lower doses reduces mannitol levels in shed oocysts. In addition, oocysts with reduced mannitol levels fail to complete the sporulation process lending further evidence for this polyol's role in the parasite.