Fabimycin likely to be an effective treatment for drug-resistant bacteria

Bacteria that cause urinary tract infections are getting more and more resistant to many medications, and they are becoming more and more difficult to cure. In ACS Central Science, scientists now describe the discovery of a novel molecule that kills drug-resistant bacteria in lab settings as well as in mice suffering from pneumonia and urinary tract infections.

Fabimycin likely to be an effective treatment for drug-resistant bacteria
Fabimycin prevents growth for over 300 strains of drug-resistant bacterial clinical isolates, including E. coli, shown in the illustration here. Image Credit: SciePro/Shutterstock.com.

The compound fabimycin, according to the researchers, may one day be utilized to treat difficult bacterial infections in people.

According to the US Centers for Disease Control and Prevention, gram-negative bacteria are a group of microbes that cause illnesses like pneumonia, urinary tract infections, and bloodstream infections in millions of people worldwide. These bacteria have powerful defensive mechanisms, including tough cell walls that keep the majority of drugs out and pumps that effectively remove those antibiotics that do get inside, making them particularly challenging to treat.

The bacteria can also change through mutation in order to resist numerous medications. Additionally, the treatments that do work are not very precise, eliminating a variety of microorganisms, even helpful bacteria. Paul Hergenrother and his team set out to create a medication that might overcome gram-negative bacteria’s defenses and treat illnesses while leaving other beneficial germs unharmed.

Starting with an antibiotic that was effective against gram-positive bacteria, the team made a number of structural changes that they thought would enable it to be effective against gram-negative infections.

While remaining largely inactive toward some gram-positive pathogens and some normally benign bacteria that reside in or on the human body, one of the modified chemicals, known as fabimycin, proved effective against more than 300 drug-resistant clinical isolates.

The novel compound also performed as well as or better than existing antibiotics at comparable doses in reducing the quantity of drug-resistant bacteria in mice with pneumonia or urinary tract infections to pre-infection levels or lower. According to the findings, fabimycin may someday be a successful treatment for challenging infections.

Source:
Journal reference:

Parker, E. N., et al. (2022) An Iterative Approach Guides Discovery of the FabI Inhibitor Fabimycin, a Late-Stage Antibiotic Candidate with In Vivo Efficacy against Drug-Resistant Gram-Negative Infections. ACS Central Science. doi.org/10.1021/acscentsci.2c00598.

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