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New candidate drug fights more than 300 resistant bacteria

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Urinary tract infections are common but are becoming increasingly difficult to treat as the bacteria that cause them become resistant to many antibiotics. Now in ACS Central Science, researchers report a new molecule that inhibits drug-resistant bacteria in lab experiments, as well as in mice with pneumonia and urinary tract infections. The researchers say this compound, fabimycin, could one day be used to treat challenging infections in humans.

Gram-negative bacteria are a class of microbes that infect millions of people worldwide, causing conditions such as pneumonia, urinary tract infections and bloodstream infections, according to the U.S. Centers for Disease Control and Prevention. These bacteria are particularly difficult to treat because they have strong defense systems: tough cell walls that keep most antibiotics out and pumps that efficiently remove the antibiotics that come in. The microbes can also mutate to escape multiple drugs. In addition, treatments that do work are not very specific, eradicating many types of bacteria, including those that are beneficial. So Paul Hergenrother and colleagues wanted to design a drug that could infiltrate the defenses of Gram-negative bacteria and treat infections, while leaving other beneficial microbes intact.

The team started with an antibiotic that was active against gram-positive bacteria and made a series of structural changes that they thought might work against gram-negative strains. One of the modified compounds, called fabimycin, was shown to be potent against more than 300 drug-resistant clinical isolates, while remaining relatively inactive against certain gram-positive pathogens and some typically harmless bacteria that live in or on the human body. In addition, the new molecule reduced the amount of drug-resistant bacteria in mice with pneumonia or urinary tract infections to pre-infection levels or below, and performed as well or better than existing antibiotics at comparable doses.

The researchers say the results show that fabimycin could one day be an effective treatment for stubborn infections.

Scientists develop new compound that kills both types of antibiotic-resistant superbugs

More information:
An iterative approach leads the discovery of the FabI inhibitor Fabimycin, a late-stage antibiotic candidate with in vivo efficacy against drug-resistant Gram-negative infections, ACS Central Science (2022). DOI: 10.1021/acscentsci.2c00598

Provided by American Chemical Society

Quote: New drug candidates fight over 300 resistant bacteria (2022, Aug. 10) retrieved Aug. 10, 2022 from https://phys.org/news/2022-08-drug-candidate-drug-resistent-bacteria.html

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