Metabolomics aided studies on drug mechanism and host-pathogen interaction in malaria

Prof. Dhanasekaran Shanmugam
CSIR-National Chemical Laboratory,
Pune | India
Part of the Symposium:
Metabolomics India - Entering the next level of population health
Metabolomics studies have facilitated many advances in the area of infectious disease biology. Much of the early studies were focused on understanding parasite biology with respect to their core carbon and energy metabolic function. Insights gained from such studies are now becoming useful for unraveling the mechanism of action of novel drugs as well as in understanding host response to pathogens and how this might affect disease outcome. In this talk, I will be discussing these aspects with respect to malaria disease and presenting our research findings. Malaria still remains endemic to many tropical countries, although malaria elimination programs, supported by WHO, have greatly reduced the overall number of malaria cases and deaths globally. One of the reasons for the persistence of malaria is the ability of the parasite (Plasmodium Sp) to become resistant to existing drugs in clinical use. This necessitates the discovery of novel antimalarial drugs. We have identified potent novel antimalarial compounds which were found to act by disrupting the mitochondrial respiratory functions by mass spectrometry metabolomics and genetics. In another study, we have used the model rodent malaria parasite P. berghei, to track the extent of metabolic dysregulation in the host by performing both targeted and untargeted profiling of serum metabolites. This study has revealed that a distinct set of metabolites are found to be altered during malaria progression. Such metabolites, in the context of human malaria, can be further studied as biomarkers for delineating between severe and benign malaria outcomes.
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