Using metabolomics to dissect host–parasite interactions
Section snippets
Background
Parasitic protozoa are an evolutionarily divergent group of unicellular eukaryotes that cause a range of important human and veterinary diseases. These pathogens often have complex life cycles, which can involve insect and mammalian hosts, as well as obligate intracellular and/or extracellular stages. While considerable progress has been made in identifying the molecular mechanisms that underlie parasite invasion of host cells and tissues and evasion of the host immune response, much less is
Studying parasite metabolism using metabolomics approaches
Analysis of intracellular metabolite pools from different parasite stages (profiling) or changes in extracellular metabolite levels during culture (footprinting) can be used to infer the operation of specific pathways and relative/absolute metabolic fluxes, respectively. Methods for rapidly quenching the metabolism of cultured parasite stages, parasite-infected host cells and isolated intracellular parasite stages have been developed [4, 5, 6••, 7, 8] as have methods for undertaking targeted or
Link between host cell range and parasite metabolic plasticity
Recent metabolomic studies on Toxoplasma gondii tachyzoite stages suggest that there is a strong link between the metabolic flexibility of intracellular parasite stages and their host range. T. gondii is one of the most successful parasites of humans, infecting nearly one third of the world's population, and other warm-blooded animals. Acute infections are caused by tachyzoite stages that can invade any nucleated cell and rapidly proliferate within a unique vacuolar compartment. Tachzyoites
Adapting a glycolytic metabolism to life in the blood
In contrast to T. gondii, a number of other parasites primarily or exclusively utilize glucose as their major carbon source and are completely dependent on glycolysis for energy generation. These include Plasmodium asexual red blood cell (RBC) stages and the T. brucei bloodstream forms (BSF) (Figure 1b,c). The dependence of these parasite stages on glucose uptake and glycolysis, with concomitant suppression of mitochondrial respiration [33, 35], likely represents an adaptation to the constant
Metabolic quiescence - an adaptive mechanism for avoiding activation of host cell anti-microbial responses?
Several obligate intracellular parasite stages enter a slow growth state and establish a silent infection with minimal activation of host cell antimicrobial responses or host cell death. This strategy is utilized by T. gondii bradyzoites [41•], Plasmodium vivax hypnozoites [42] and Leishmania amastigotes [43], which reside within vacuolar compartments in neuronal and muscle cells, liver cells, and different phagocytic cells, respectively. It is often difficult (or impossible) to generate
Conclusions
Metabolomic approaches are beginning to highlight differences as well as common features of the central carbon metabolism in different parasite species and developmental stages that were not anticipated from genomic or transcriptomic studies. These studies suggest that, far from having an invariant, house-keeping function, parasite central carbon metabolism plays a key role in allowing these pathogens to adapt to different nutrient conditions and/or other stresses encountered in different host
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank all members of the McConville lab for discussions. MJM is an NHMRC Principal Research Fellow.
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