Starving malaria?

Microscope image of red blood cells containing Plasmodium falciparum parasites. Credit: United States Department of Health and Human Services United States Department of Health and Human Services via Wikimedia Commons.

Malaria is one of the most common and deadly tropical diseases, causing a wide range of symptoms, including brain damage and, in the most severe cases, coma  (known as “cerebral malaria”). It is produced by a species of parasites known as Plasmodium, which are passed to humans by blood-feeding mosquitoes. The latest estimates from the World Health Organization indicate that in 2015 there were 214 million new malaria cases in tropical regions of the globe, with almost half a million deaths due to complications arising from infection. Interestingly, malaria-infected patients admitted to hospital show an increase in the number of parasites in the blood when they resume eating, especially after they have experienced famine. This puzzling observation led the scientific community to ask whether malaria parasites are capable of sensing how much food is available to them, and coordinate their replication and virulence accordingly? This question has been recently addressed by a team of scientists led by Dr Maria Mota, from the University of Lisbon, who has been able to recapitulate the clinical observations in experimental infections in mice.

By using mice subjected to low caloric intake regime (known as caloric restriction), the researchers found that Plasmodium parasites replicate at a significantly lower rate, and produce fewer symptoms (e.g. cerebral malaria), when compared to animals that had a normal caloric intake (fed ad libitum – or ‘feeding freely’). Excitingly, the team also found that the mice with a low-caloric intake survived, on average, 3 times longer than mice fed ad libitum. On the other hand, when caloric-restricted mice were fed again with glucose, thus restoring the levels of this nutrient in blood, the effects on Plasmodium growth and virulence were reverted, indicating that these parasites can actively sense and respond to nutrient availability.

Interestingly, the researchers found that an energy-sensing system controlling energy levels in the cell, highly conserved in practically all living organisms, also operates in Plasmodium parasites. A key regulator of this system is a protein known as KIN, which activity is stimulated by nutrients such as glucose, but not by vitamins or minerals. The researchers found that when the gene encoding for this protein was deleted, or “knocked out”, Plasmodium parasites multiplied equally in caloric-restricted and normally-fed mice. Moreover, when this gene was reintroduced in the mutant parasites lacking the gene for KIN, they became susceptible to nutrient availability, and at the same time responded to caloric restriction by adjusting their multiplication rates, as was observed in unmodified, or “wild type” parasites. Altogether, these experiments demonstrate that the energy-sensing system controlled by KIN is essential for Plasmodium multiplication and infectiveness.

These remarkable studies put forward the possibility of targeting the parasite nutrient-sensing mechanisms; although further characterisation is required to decipher exactly how differently the energy-sensing mechanism operates between parasites and their hosts, like humans. Similarly, these finding open new avenues to understand how the replication of the malaria parasite can be modulated and weakened, with important implications for its ability to cause disease and to be transmitted to new patients.


This article was written by Juan Quintana and edited by Bonnie Nicholson.

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