Authors: Martha Powell, Future Science Group
A new study has demonstrated that the malaria parasite, Plasmodium, has the ability to sense and actively adapt to the host’s nutritional status, with mice eating fewer calories possessing a significantly lower parasitic load.
The team, led by Maria Mota, from Instituto de Medicina Molecular in Lisbon, Portugal, identified two possible explanations for this observation. Either the parasite was actively adapting in response to hosts with lower calorie intake, or the pathogen was struggling to replicate as a result of lacking key nutrients.
The researchers utilized a mouse model to investigate, controlling food intake of mice before infection with Plasmodium, initially discovering that mice eating 30% fewer calories had a significantly lower parasite load.
Mota commented: “This finding alters our understanding of the dynamics of malaria infections in the field and might be highly relevant facing the alarming trend of global increased overweight versus underweight populations, including in malaria endemic regions.”
Kinome analysis, combined with chemical and genetic approaches, were then used to identify proteins that may be regulating this pathway. The team discovered parasites that lacked the enzyme KIN had impaired responses to decreased nutrient availability, replicating at the same rate regardless of calorie intake. These findings implicate KIN as a nutrient sensor and key regulator of the parasite’s ability to respond to nutritional alterations.
Author Manuel Llinás (Penn State University, PA, USA) explained: “This is one of the best examples demonstrating that malaria parasites sense and adapt to their host’s metabolic environment through transcriptional and developmental changes. Discovering precisely how this occurs may lead to new therapeutic intervention strategies to significantly reduce parasite burden.”
This study is the first to reveal that parasite’s adapt to their host’s nutritional status via transcriptome rearrangement, directly affecting their replicative rate and virulence. Further research will investigate the mechanisms behind KIN, and the team hope that in the future, targeting this pathway could provide novel therapeutic approaches.
Collaborator, Oliver Billker (the Wellcome Trust Sanger Institute, Cambridge, UK) concluded: “This is the first time that anyone has seen that a parasite can actively restrict its growth to the environment and completely changes the way we look at parasite growth. While future research is still necessary to understand the full extent of these findings, it may well have implications not just for malaria, but also for other infectious diseases.”
Sources: Manico-Silva L, Slavic K, Ruivo MTG et al. Nutrient sensing modulates malaria parasite virulence. Nature. doi:10.1038/nature23009 (2017) (Epub ahead of print); www.eurekalert.org/pub_releases/2017-07/idmm-lib070517.php