Targeting the malaria parasite: from lab innovation to new interventions

It is unusual, at an EDCTP Forum, for a plenary session to feature a presentation on laboratory research. Indeed presenter Professor Maria Mota emphasised that her work has not as yet involved human subjects. Nevertheless, many of those present were impressed by the potential implications of her findings.

Professor Mota works at Lisbon’s Instituto de Medicina Molecular, situated close to the Forum venue. Her presentation was entitled ‘Targeting the malaria parasite: from lab innovation to new interventions’. Her focus was on the behaviour of the malarial parasite once it reaches the hepatocyte cells in the liver, where it is known to replicate rapidly. Working on mice (using the parasite Plasmodium berghei) she sought to determine which factors make possible replication on such an enormous scale.

Proteins in the membranes of the hepatocyte play a key role; the UIS3 protein has been shown to block the parasite. The role of lipids is also important. The parasite has a need for lipids, therefore, Dr Mota wondered whether a mouse given a high-lipid diet might be more vulnerable to the effects of the parasite. She was, however, surprised to find that on such diet, given at the time the infection takes place, disease onset was later and survival greater. This led her to ask a bigger question – whether (and how) dietary alterations modulate susceptibility to Plasmodium infection. In a study published last year, her team was able to show that show that administration of a high-fat diet to mice for a period of only four days impaired Plasmodium liver infection by over 90%; the sporozoites could successfully invade and initiate replication, but died inside the hepatocytes and were therefore unable to cause severe disease. Analyses revealed that this impairment of infection was mediated by oxidative stress; reactive oxygen species (ROS) directly impact on Plasmodium survival inside hepatocytes.

This in turn has led on to other questions that she is trying to answer. These include whether African populations might have evolved genetic protection against malaria that involves ROS, in a way that would be comparable to the development of the sickle cell trait.

She also continues to pursue the notion that parasites can ‘sense’ the nutrients in their environment and make a response to this that modulates their virulence. Another paper last year has produced some interesting findings. Caloric restriction of the diet of the mice in the study was linked to a reduction in both parasite replication and virulence. (This work also echoes findings in other disease areas that individuals on a calorie restricted diet live longer lives!)

Professor Mota received several questions from the floor of the meeting, and indeed later on. She was congratulated for her work, with many saying that it would be important to find out more about the mechanisms involved in the process by which changes in the diet of a host impact on the replication and virulence of the parasite.

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