When you think of the causes of infectious diseases, what first comes to mind are probably viruses and bacteria. But parasites are another important source of devastating infection, especially in the developing world. Now, NIH researchers and their collaborators have discovered a new kind of treatment that holds promise for fighting parasitic roundworms. A bonus of this result is that this same treatment might work also for certain deadly kinds of bacteria.
The researchers identified the potential new therapeutic after testing more than a trillion small protein fragments, called cyclic peptides, to find one that could disable a vital enzyme in the disease-causing organisms, but leave similar enzymes in humans unscathed. Not only does this discovery raise hope for better treatments for many parasitic and bacterial diseases, it highlights the value of screening peptides in the search for ways to treat conditions that do not respond well—or have stopped responding—to more traditional chemical drug compounds.
Humans, parasites, and bacteria depend on the same cellular pathway to break down glucose for energy. This life-sustaining metabolic pathway includes essentially all of the same enzymes with one notable exception: cofactor-independent phosphoglycerate mutase (iPGM). This enzyme is found in parasites and bacteria, but not in people. Yes, we humans have an enzyme that does that same job—but it does so in a different way and is assembled from an entirely different sequence of amino acid building blocks.
Given this very exploitable difference, iPGM jumped several years ago to the top of the list as a drug target that would kill disease-causing parasites without harming people.
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