A new perspective on the relationship between Entamoeba histolytica and enteropathogenic bacteria: the role of queuine as a nutritional regulator of Entamoeba histolytica virulence

Entamoeba histolytica is a unicellular parasite that can phagocytose colonic bacteria in the human gut. Most infected individuals are asymptomatic but for unknown reasons, the parasite can become virulent and invasive, causes amebic dysentery, and migrates to the liver, where it causes hepatocellular damage. This pathogenic process is marked by acute inflammation. The triggers that cause E. histolytica to become more virulent have been investigated for the last few decades and it has become evident that E. histolytica`s pathogenicity is directly linked to the parasite`s interaction with the gut microbiota. However, it is not yet clear what is the nature of this interaction. Here, we will present evidences supporting a role of enteric bacteria in shaping the response of the parasite exposed to oxidative stress (OS).

Lower and higher eukaryotes are supplied with queuine (Q) by the intestinal flora. Q which is efficiently incorporated in E.histolytica’s tRNAs leads to significant hypermethylation of C38 in tRNAAsp-GTC and triggers resistance of the parasite to OS. We have biochemically characterized the parasite’s tRNA-guanine transglycosylase (TGT), the enzyme that catalyzes the Q modification of tRNAs. EhTGT is predominantly a cytoplasmic protein. EhTGT silenced trophozoites have a growth defect. The characterization of additional phenotypical traits is under progress. Surprisingly, Q leads to significant change in the parasite’s transcriptome and it induces the expression of stress response proteins, chaperone and oxidoreductase. These results indicate that Q prepares the parasite to resist OS by turning on the expression of genes involved in stress response.