Submitted to: Journal of Medical Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/9/2000
Publication Date: N/A
Citation: N/A Interpretive Summary: Entamoeba histolytica, which causes dysentery and liver abscesses, does not undergo oxidative respiration typical for such eukaryotes. They lack enzymes for oxidative-phosphorylation and instead possess fermentation enzymes resembling those of obligately anaerobic bacteria. We do not know whether this parasite recently acquired such fermentation enzymes from bacterial donors, or whether instead they have retained fermentation enzymes subsequently lost by most other eukaryotes. I reconstructed the evolutionary relationships of two fermentation enzymes from Entamoeba histolytica to homologues present in other protozoan parasites to determine whether they are distinct from those in bacteria. The analysis suggests that protozoan parasites acquired these fermentation enzymes independently from different bacteria, and specifies the likely donors of each. This study further erodes the notion that fermenting eukaryotic parasites are ancient relicts of an era before eukaryotes acquired the means to undergo oxidative phosphorylation. Together with previous studies of our own and by others, the data suggest that E. histolytica descends from an ancestor that once used mitochondria to undergo oxidative metabolism, and that they acquired from bacteria the genes that enable them to live in environments where oxygen is scarce. The challenge for future studies is to determine the mixture of gene losses and gains and protein modifications, which allow lumenal parasites to adapt to their anaerobic niche and cause disease.
Technical Abstract: Entamoeba histolytica is a eukaryote which survives in the colonic lumen and in tissue abscesses by means of fermentation enzymes that resemble those of anaerobic bacteria. The goals herein were to determine the origin of three genes in E. histolitica encoding fermentation enzymes (malic enzyme and two alcohol dehydrogenases (ADHE and ADH1)) and to compare amebic fermentation products to those of anaerobic bacteria. Phylogenetic trees of malic enzymes strongly suggested the amebic gene was horizontally transferred from an archaebacterium, as has been shown for the amebic ferredoxin gene. Phylogenetic analyses also suggested amebic genes encoding ADH1 and ADHE were horizontally transferred from gram-positive bacteria. Although the activity of ADH1 greatly exceeds that of ADHE and ADH3, supernatants of amebae contained ethanol (the fermentation product of ADHE) and acetate but lacked isopropanol, acetone, or butanol (theoretical products of ADH1 and ADH3). Cultured amebae express a gene encoding an iron-dependent hydrogenase, which was active as a recombinant protein. We conclude that amebic genes encoding numerous fermentation enzymes were horizontally transferred from anaerobic bacteria, even though the parasite fermentation products (ethanol, acetate, and CO2) resemble those of yeast.