Around one people on the planet are infected with parasitic helminths, round worms that live in soil and colonize human guts through dirty water. The helminths owe their ability to survive in the low oxygen environment of the human gut to a unique enzyme variant, Donnelly Centre researchers have found.
The findings raise hopes of new treatments to quell growing resistance of parasites to available medications. Infections are common in less developed countries where they can leave long-lasting consequences on child development.
“When parasites are outside the body, which they are for a part of their lifecycle, they breathe oxygen just like we do,” says Andrew Fraser, a senior author and a professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at U of T’s Faculty of Medicine. “We were trying to understand how these parasites survive inside the human gut where there’s almost no available oxygen.”
The study was also co-led by Gustavo Salinas, a professor at Universidad de la República in Uruguay, and Jennifer Shepherd, a professor at Gonzaga University in the U.S.
The findings have been published in e-Life, an online journal for life-sciences.
Most animals, including humans, make energy through aerobic, or oxygen-dependent metabolism, with the help of a molecule called ubiquinone, or UQ. When they are inside their host, parasitic helminths switch to an unusual type of anaerobic metabolism that burns a related molecule called rhodoquinone, or RQ.
In their previous study, Fraser’s team uncovered that UQ and RQ are made from different precursor molecules by the same enzyme called COQ2. But how does COQ2 know to use the UQ precursor when there’s oxygen around but use the RQ precursor when there’s no oxygen?
“Somehow there has to be a switch,” says Fraser. “If we could understand how that switch works and if we could take a small compound and interfere with that switch, prevent it from making RQ, that might be a way to kill a parasite in humans.”[…]