Multitarget Drugs to Challenge Microbial Resistance

A group of purple, rod-shaped bacterial cells rendered by computer at Centers for Disease Control and Prevention by Melissa Brower.
Computer-generated image of drug-resistant Mycobacterium tuberculosis bacteria. Credit: Melissa Brower, Centers for Disease Control and Prevention.

Drugs that target a single essential protein in a microbial invader can be effective treatments. But the genomes of pathogens—including bacteria, fungi and parasites—mutate rapidly, and resistance can develop if a mutation changes a target protein’s structure. Molecules that interfere with multiple microbial proteins at once have the potential to overcome the growing problem of antimicrobial drug resistance.

Researchers led by Eric Oldfield exit icon of the University of Illinois recently explored whether an experimental drug called SQ109, developed to treat tuberculosis (TB), could be tweaked to attack multiple enzymes, as well as to kill different types of microbes. The scientists succeeded in creating several multitarget analogs of SQ109 that were more effective than the original drug at killing their target pathogens in laboratory experiments. These analogs included one compound that was five times more potent against the bacterium that causes TB while also being less toxic to a human cell line tested.

This work was also funded by the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases and the NIH Office of the Director.

Learn more:
University of Illinois, Urbana-Champaign News Release exit icon

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