Decay of the glycolytic pathway and adaptation to intranuclear parasitism within Enterocytozoonidae microsporidia

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Glycolysis and oxidative phosphorylation are the fundamental pathways of ATP generation in eukaryotes. Yet in microsporidia, endoparasitic fungi living at the limits of cellular streamlining, oxidative phosphorylation has been lost: energy is obtained directly from the host or, during the dispersive spore stage, via glycolysis. It was therefore surprising when the first genome from the Enterocytozoonidae – a major family of human and animal-infecting microsporidians - appeared to have lost glycolysis. Here we sequence and analyse genomes from four additional members of this family, shedding new light on their unusual biology. Our survey includes the genome of Enterocytozoon hepatopenaei, a major aquacultural parasite currently causing substantial economic losses in shrimp farming, and Enterospora canceri, a pathogen that lives exclusively inside the nuclei of its crab host. Our analysis of gene content across the clade suggests that Ent. canceri’s adaptation to intranuclear life is underpinned by the expansion of transporter families. We demonstrate that this entire lineage of pathogens has lost glycolysis and, uniquely amongst eukaryotes, lacks any obvious intrinsic means of generating energy. Our study provides an important resource for the investigation of host-pathogen interactions and reductive evolution in one of the most medically and economically important microsporidian lineages.This work was supported by Royal Society University Research Fellowships (B.A.P.W. and T.A.W.) and by a University of Exeter/Cefas strategic alliance studentship (DWB). AP and KS would like to acknowledge support from the Agricultural Research Development Agency (Arda) of Thailand (Grant number 8669), Mahidol University and the National Center for Genetic Engineering and Biotechnology (BIOTEC) of the Thai National Science and Technology Development Agency (NSTDA). OI is supported by Mahidol University. PJ is supported by Science Achievement Scholarship of Thailand (SAST)