• Posted July 25, 2024

'Two-Target' Antibiotics Could Make Bacterial Resistance Much Tougher

Synthetic antibiotics that attack bacteria in two directions at once could be the solution for combatting antimicrobial-resistant bugs, a new study claims.

These dual-action antibiotics, called macrolones, disrupt bacterial cell function in two different ways.

It’s nearly impossible for bacteria to resist macrolones, because the germ would need to defend against both attacks at once, researchers said.

“The beauty of this antibiotic is that it kills through two different targets in bacteria,” said researcher Alexander Mankin, a distinguished professor of pharmaceutical sciences at the University of Illinois Chicago (UIC).

“If the antibiotic hits both targets at the same concentration, then the bacteria lose their ability to become resistant via acquisition of random mutations in any of the two targets,” Mankin explained in a university news release.

Macrolones combine the structures of two widely used antibiotics:

• Macrolides like erythromycin which block ribosome, the protein-manufacturing factories inside a bacteria cell.

• Fluoroquinolones like ciprofloxacin that target the enzymes bacteria need to replicate.

Lab experiments at the University of Illinois Chicago found that macrolones could simultaneously attack both targets, while also failing to trigger the activation of any bacterial resistance genes.

“By basically hitting two targets at the same concentration, the advantage is that you make it almost impossible for the bacteria to easily come up with a simple genetic defense,” said researcher Yury Polikanov, an associate professor of biological sciences at UIC.

The new study was published July 22 in the journal Nature Chemical Biology.

“The main outcome from all of this work is the understanding of how we need to go forward,” Mankin said. “And the understanding that we’re giving to chemists is that you need to optimize these macrolones to hit both targets.”

More information

The U.S. Centers for Disease Control and Prevention has more about antimicrobial resistance.

SOURCE: University of Illinois Chicago, news release, July 23, 2024