Mitochondrial glycolysis as a target for disease control of pathogenic stramenopiles

The world population is expected to grow to 10 billion people in the next 30 years. This means that we will have to feed 2 billion more people than we do today. This will put a huge strain on our food production systems. A major problem for agriculture and fisheries is the losses caused by infectious diseases. Although they vary from year to year, these crop losses could have fed between 0.5 and 4 billion people each year. Some of the potato and salmon diseases are caused by a group of pathogens in which we have discovered an unusual biochemical feature. We are now characterising this unusual feature in the hope that it will lead to a new drug that could combat some of the pathogens that cause major losses in our food production.

Disease seriously affects humans, animals and plants. In the case of livestock and crops, such diseases impact on the provision of food. The world population is expected to reach 9 to 10 billion within the next 30 years, so we need to produce more food than we currently do. Diseases therefore limit our ability to produce the food we need. We recently discovered a peculiar feature in a large group of organisms, which include several pathogens of humans, animals and crops. Normally, the food we consume is broken down in simple compounds such as the sugar glucose. This glucose is metabolised into smaller molecules leading to the production of the energy molecule ATP. This breakdown of glucose happens in the main compartment of the cell called the cytoplasm, while the bulk of the ATP production takes place in a special compartment called the mitochondrion. We discovered that in some organisms the breakdown of glucose takes place in the ATP-producing mitochondria. This is quite unexpected and raises the question what the reason is for this peculiarity. In addition, this also means that a different molecule needs to be transported into the mitochondrion to make this possible. As this transport is normally tightly controlled by very special transporters, this means that a special transporter will be required to make sure the energy provision of these organisms can take place. We aim to identify and characterise this special transporter with the aim to use it as a new drug target. This drug target is present in a human intestinal parasite and also in important animal and plant pathogens, and would allow for the specific targeting of these pathogens while not affecting their hosts. Our project will elucidate the nature of this unusual metabolic phenomenon and provide insight in the evolution and biochemistry of this transporter with the aim to produce novel therapeutics to combat important pathogens.