Metabolomics in the fight against malaria

Abstract

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

“…Metabolomics represents a powerful analytical approach to uncover the activity of physiological and pathological processes (Li et al, 2016) for the discovery of biomarkers of infectious diseases, including malaria (Park et al, 2015; Salinas et al, 2014). Nuclear magnetic resonance or gas/liquid chromatography coupled with mass spectrometry (GC/LC-MS) have been applied to understand the metabolic changes in models of host- Plasmodium interactions in vitro (Lakshmanan et al, 2012; MacRae et al, 2013; O’Hara et al, 2014; Olszewski et al, 2009; Park et al, 2015; Sana et al, 2013) and in vivo (Basant et al, 2010; Ghosh et al, 2012, 2013; Olszewski et al, 2009; Sengupta et al, 2013; Tritten et al, 2013).…”

What was old is new again: using the host response to diagnose infectious disease

“…Progress has been made in sepsis diagnosis and prognosis; differentiating viral, bacterial and fungal pathogen classes; and presymptomatic diagnosis. Advances in understanding and diagnosing diverse pathogens including early Lyme disease [175], malaria [176] and Dengue fever [177,178] are being forged using the host response. However, much work remains to be done with respect to discovering new host-derived biomarkers as well as advancing existing biomarkers through the development pipeline.…”

Malaria vaccine clinical trials: what's on the horizon

“…Such endeavors require major resource investment, but are necessary to capitalize on the extreme benefits of current technologies and move towards systems biology approaches for discovery. The Malaria Host-Pathogen Interaction Center (MaHPIC, http://www.systemsbiology.emory.edu/) is an example of a multi-institutional consortium uniquely created to use systems biology approaches to investigate and compare malaria in both humans and non-human primates [62,63]. This consortium is generating unprecedented ‘omics and immune-profiling datasets, for eventual online distribution to the research community, using systems biology tools and several non-human primate - parasite infection combinations as models of malaria.…”