Fig 1.
Nucleotide acquisition and metabolism in host cells and microsporidia.
Schematic illustration showing nucleotide metabolism in a typical microsporidian parasite within an infected host cell. Host cells can make nucleotides via de novo biosynthesis and regenerate ATP by oxidative phosphorylation—these pathways are absent in microsporidia [5]. Host purine nucleotides can be stolen using microsporidia NTT transporters and then efficiently used and recycled by the parasites [18]. Key: (a) E. cuniculi physically tethers mitochondria using an unidentified protein [49]. (b) Only EcNTT3 of E. cuniculi has been found in the mitosome [38]. (c) Nematocida may secrete a hexokinase into the host cell to stimulate host nucleotide production [6]. (d) Nucleoside kinases are apparently absent from some microsporidian genomes but are present in Trachipleistophora hominis [18]. (e) Thymidine kinase is present in some microsporidia but not all [18]. (f) The microsporidian RNA degradation pathway is shown in S2 Fig.
Fig 2.
Nucleotide biosynthesis in microsporidia.
(A) Nucleotide biosynthetic enzymes found in the genomes of yeast, Escherichia coli, Microsporidia, and intracellular pathogenic bacteria for purine (red) and pyrimidine (green) metabolism according to the KEGG database [60] are shown along with respective EC numbers (see S3 Fig). Sc = Saccharomyces cerevisiae; Th = Trachipleistophora hominis; Ec = Encephalitozoon cuniculi; Ct = Chlamydia trachomatis; Rr = Rickettsia rickettsii. (B) Purine and pyrimidine pathways retained in microsporidia genomes (black arrows) enable recycling of all of the major nucleotides based on available genome data [18]. Some exceptions to the general rule can be found in (a) T. hominis or (b) N. ceranae, as described in the text.
Fig 3.
Key metabolic steps lost by microsporidia and intracellular bacteria.
Several key enzymes and the associated pathways are shown that have been lost during microsporidian evolution (green square). The implications for the parasites are shown to the right. With the exception of PRPP synthase, all enzymes have been lost by obligate intracellular bacterial pathogens (green square). Exceptions: (a) nucleoside kinases are retained in T. hominis