Niche metabolism in parasitic protozoa

Abstract

Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generated in silico has been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism.

Figure 1

Complex interactions can occur between protozoan parasites and (a) host and vector or (b) host and environment. ^aRogers et al. (2004).

Figure 2

A comparison of energy metabolism in (a) bloodstream form T. brucei and (b) procyclic (insect form) T. brucei. (a) Bloodstream T. brucei, although an obligate aerobe, produces a net gain in ATP only through the cytoplasmic substrate-level phosphorylation catalysed by pyruvate kinase. The figure shows the compartmentalization of glycolysis between glycosomes and cytoplasm; the mitochondrion does not contribute directly to ATP production. ATP synthase operates in the direction of ATP hydrolysis to generate a proton motive force. A partial respiratory chain complex I enzyme (NADH : ubiquinone oxidoreductase, denoted I in the figure) oxidizes NADH generated in the mitochondrial matrix, but does not contribute to proton-pumping across the inner mitochondrial membrane. There is no classical respiratory chain; the terminal oxidase is alternative oxidase (AOX). Intraglycosomal redox balance is maintained using a glycerol-3-phosphate dehydrogenase (GPD) shuttle. The additional enzyme in this scheme is 1, phosphoglycerate kinase. Other abbreviation: Q, ubiquinone. (b) In procyclic trypanosomes, the organization and compartmentalization of energy metabolism is more complex. Enzymes discussed in the text and additional to those listed in (a) are as follows: 2, fructose-1,6-bisphosphatase; 3, glycosomal fumarate reductase; 4, pyruvate phosphate dikinase; 5, acetate : succinate CoA transferase; 6, succinyl-CoA synthetase; 7–8, mitochondrial NADH dehydrogenases distinct from rotenone-sensitive complex I; 9, mitochondrial fumarate reductase; 10, phosphoenolpyruvate carboxykinase; 11, glycosomal malate dehydrogenase. Other abbreviations: II, succinate dehydrogenase (complex II); III, cytochrome c reductase (complex III); IV, cytochrome c oxidase (complex IV); c, cytochrome c. It is not known whether mitochondrial oxidation of fatty acids (by far the most efficient substrate in terms of amount of ATP that can be generated per carbon molecule oxidized to CO₂) contributes to energy generation in African trypanosomes. End-products of energy metabolism are highlighted in bold.

Figure 2

A comparison of energy metabolism in (a) bloodstream form T. brucei and (b) procyclic (insect form) T. brucei. (a) Bloodstream T. brucei, although an obligate aerobe, produces a net gain in ATP only through the cytoplasmic substrate-level phosphorylation catalysed by pyruvate kinase. The figure shows the compartmentalization of glycolysis between glycosomes and cytoplasm; the mitochondrion does not contribute directly to ATP production. ATP synthase operates in the direction of ATP hydrolysis to generate a proton motive force. A partial respiratory chain complex I enzyme (NADH : ubiquinone oxidoreductase, denoted I in the figure) oxidizes NADH generated in the mitochondrial matrix, but does not contribute to proton-pumping across the inner mitochondrial membrane. There is no classical respiratory chain; the terminal oxidase is alternative oxidase (AOX). Intraglycosomal redox balance is maintained using a glycerol-3-phosphate dehydrogenase (GPD) shuttle. The additional enzyme in this scheme is 1, phosphoglycerate kinase. Other abbreviation: Q, ubiquinone. (b) In procyclic trypanosomes, the organization and compartmentalization of energy metabolism is more complex. Enzymes discussed in the text and additional to those listed in (a) are as follows: 2, fructose-1,6-bisphosphatase; 3, glycosomal fumarate reductase; 4, pyruvate phosphate dikinase; 5, acetate : succinate CoA transferase; 6, succinyl-CoA synthetase; 7–8, mitochondrial NADH dehydrogenases distinct from rotenone-sensitive complex I; 9, mitochondrial fumarate reductase; 10, phosphoenolpyruvate carboxykinase; 11, glycosomal malate dehydrogenase. Other abbreviations: II, succinate dehydrogenase (complex II); III, cytochrome c reductase (complex III); IV, cytochrome c oxidase (complex IV); c, cytochrome c. It is not known whether mitochondrial oxidation of fatty acids (by far the most efficient substrate in terms of amount of ATP that can be generated per carbon molecule oxidized to CO₂) contributes to energy generation in African trypanosomes. End-products of energy metabolism are highlighted in bold.