LONDON ¿ The genome of a single-celled parasite that afflicts immunosuppressed people, as well as many pets, was published last week, opening the door for the development of new drugs and diagnostic tools to tackle it. Researchers in France say its genome has been stripped down to the bare essentials required to allow it to infect and reproduce in host cells.
The parasite, Encephalitozoon cuniculi, belongs to the group of intracellular parasites known as the Microsporidians. Details of its genome will help biologists settle the debate about whether the Microsporidia are highly evolved fungi or ancient eukaryotes. The genomic information also will yield insights into the unusual metabolic pathways that characterize these organisms.
Christian Vivares, professor of molecular parasitology at the University Blaise Pascal in Aubiere, France, told BioWorld International: ¿We hope that new drugs to treat this infection will eventually be developed, because we identified several metabolic pathways that are unique to this organism. We suspect that some other intracellular parasites use the same metabolic pathways, and we are researching whether these would make good therapeutic targets in Plasmodium, for example.¿
Vivares, together with colleagues at the university and at Genoscope in Evry, France, and at the University of Lyon in Villeurbanne, France, reported the results of the sequencing effort in a letter to Nature titled ¿Genome sequence and gene compaction of the eukaryote parasite Encepahlitozoon cuniculi.¿
Commenting on the paper in a News & Views article in Nature, Patrick Keeling, of the University of British Columbia in Vancouver, wrote that the genome of E. cuniculi is a ¿treasure trove of information on the powerful reductive forces that shape these unusual parasites.¿ In his article, titled ¿Parasites go the full monty,¿ he said that the French team has ¿already identified several genes that strongly support a fungal origin for these parasites.¿
E. cuniculi is a eukaryote that parasitizes other eukaryotes. An obligate intracellular parasite, it can survive only in the cells of its hosts, which include cattle, mice, rabbits and humans.
In humans, E. cuniculi and related Microsporidia are responsible for some of the opportunistic infections suffered by people with AIDS and transplant recipients taking immunosuppressive drugs. In those with AIDS, for example, Microsporidia cause about a third of bouts of diarrhea.
It also is to blame for some cases of diarrhea and some corneal infections in immunocompetent people. In developed countries, up to 38 percent of people have antibodies to Microsporidia. Spores of Microsporidia can be spread in contaminated drinking water, or may be passed on by pets with diarrhea.
Vivares said his team decided to sequence the genome of E. cuniculi partly because it has the smallest genome of all the intracellular parasites. He said: ¿Its genome is smaller than Plasmodium, Toxoplasma, Leishmania and Trypanosoma, which are the causes of malaria, toxoplasmosis, leishmaniasis and trypanosomiasis, respectively, and so we thought it would be a good model.¿
Among the surprising features of the parasite¿s genome, Vivares said, was the discovery that many genes were smaller than their counterparts in other organisms. ¿The missing regions could be involved in the fine regulation of genes that you find in free-living organisms. For biotechnology applications, it will be important to analyze these proteins, which could form models for the development of peptides that could interact with targets involved in pathological processes.¿
The genome of E. cuniculi is only 2.9 million base pairs long, less than 0.1 percent of the size of the human genome, and smaller than that of many bacteria. It has fewer than 2,000 sequences thought to code for proteins, and there is very little ¿junk DNA¿ between these stretches.
Each ¿gene¿ is also shorter than its counterparts in other species. Vivares and his colleagues found that many of E. cuniculi¿s genes were on average about 14 percent shorter than the equivalent genes in yeast.
One of the most intriguing findings for parasitologists is the discovery of 22 genes involved in metabolism that normally takes place in mitochondria ¿ the cellular organelles that convert food into energy. Microsporidia are thought not to have mitochondria, or rather, if they do, no one knows what they look like. Vivares said, ¿it appears that many genes are involved in mitochondrial pathways and could be localized in an organelle acting as a residual mitochondrion.¿
Keeling says the debate about whether Microsporidia have lost their mitochondria or whether scientists have simply failed to recognize their mitochondria has deepened with the publication of the genome. He writes that it is not clear from the genes alone whether those that encode for what appear to be mitochondrial metabolic enzymes operate in a mitochondrion or whether they have been relocated to the cytoplasm. He adds: ¿There is credible evidence either way, but in this case the gene sequences only raise the questions. The answers await the localization of the enzymes within the cell.¿