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Enterocytozoon bieneusi  is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia,  E. bieneusi  is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of  E. bieneusi  have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for  E. bieneusi . Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in  E. bieneusi , of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of  Encephalitozoon cuniculi  proteins. Only one  E. bieneusi  protein with assigned function had no  E. cuniculi  homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the  E. bieneusi  genome, all traits consistent with genomic compaction. Our findings suggest that  E. bieneusi  is a likely model for extreme genome reduction and host dependence.

Genomic Survey of the Non-Cultivatable Opportunistic Human Pathogen, Enterocytozoon bieneusi