Nutrient sensing modulates malaria parasite virulence

Authors:
Top Cited Papers
Open Access
Publisher website
Google Scholar
Abstract
Malaria parasites use a sensing mechanism to moderate their growth in response to the nutrient content of their host. The ability of pathogens to sense and respond to their environment is essential for their virulence and survival. In this study, Maria Mota and colleagues report the discovery that malaria parasites use a sensing mechanism to moderate growth in response to the nutrient content of blood plasma. Malaria parasites actively respond to changes in their host's dietary calorie intake through a rearrangement of their transcriptome, which is accompanied by a change in their replication rate. The authors identify the kinase KIN, which shares homology with the conserved SNF1/AMPKα kinases in mammalian cells and yeast, as a key regulator of the parasite's response to nutrient fluctuations. This work not only reveals a hitherto unknown nutrient-sensing mechanism in Plasmodium parasites, but also identifies KIN as a potential therapeutic target for malaria interventions. The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions1,2. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium3,4,5, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.

This publication has 39 references indexed in Scilit: