Research teams led by the National Institutes of Health's National Center for Advancing Translational Sciences and the University of Tokyo have discovered an inhibitor of an enzyme found in both parasites and bacteria. The discovery could result in new treatments for both parasitic and bacterial infections, according to a new study published in the journal Nature Communications.
The enzyme — cofactor-independent phosphoglycerate mutase — is essential for the survival of parasites known as roundworms, but is not carried by humans, making it a potential treatment target. The parasitic round worms afflict approximately 150 million people across 80 countries and can cause severe infectious diseases, which can harm the skin and eyes sometimes resulting in blindness. The enzyme can also be found in the bacteria Staphylococcus aureus, which is responsible for causing the hospital-acquired infection methicillin-resistant Staphylococcus aureus.
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To identify an inhibitor for the enzyme, researchers sorted through 1 trillion protein fragments known as cyclical peptides. Researchers identified two protein fragments that bound tightly to the iPGM enzyme and shut down its activity.
"Several infectious organisms are potentially susceptible to an iPGM inhibitor," said co-corresponding author James Inglese, PhD, director of the NCATS assay development and screening technology laboratory. "The team dubbed the inhibitor peptides 'ipglycermides,' which represent a powerful class of iPGM inhibitors. In theory, such a drug could become a broad spectrum anti-parasitic and antibacterial treatment."
Current medications to treat round worm infections are only effective when the worm is in its larval stages, meaning treatment must be regularly administered annually or semiannually for as long as 10 years. The iPGM inhibitor may result in a more efficient treatment that would be effective in all stages of the worm's life.
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