Dissection of the Leishmania mannogen biosynthetic pathway: beta 1-2 mannan in pathogens and beyond

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Most living organisms store energy reserves in the form of glucose-based polysaccharides; glycogen in humans, and starch in plants, for example. But some organisms use more unusual forms of carbohydrate storage. As part of an international team, we have just discovered the Leishmanial parasite - the causative agent of the sandfly-transmitted Leishmaniases, for example, stores energy in the form of an unusual polysaccharide termed 'mannogen'. Formation of this energy store is essential for the parasite infectivity. This grant will investigate how mannogen is made and broken down by Leishmania. We will dissect exactly how enzymes, nature's catalysts, are used to make this energy store and see if the enzymes can be inhibited in order to provide the academic foundation for potential new anti-parasite agents. Around two million people each year contract this debilitating disease and around seventy thousand will die. Our research will provide insights into the metabolism into this major world parasite. Beyond this, our work shows that similar enzymes exist across bacteria, our work will probe their structure and function and hopefully identify new biochemical pathways in a range of bacteria.