Labmanager Logo
a 3d rendered image of microscopic blue and red bacteria of various shapes on a light blue background

iStock, fatido

Dual Action Antibiotic Could Make Bacterial Resistance Nearly Impossible

Synthetic antibiotics called macrolones work by disrupting two different cellular targets

| 2 min read
Share this Article
Register for free to listen to this article
Listen with Speechify
0:00
2:00

A new antibiotic that works by disrupting two different cellular targets would make it 100 million times more difficult for bacteria to evolve resistance, according to new research from the University of Illinois Chicago.

For a new paper in Nature Chemical Biology, researchers probed how a class of synthetic drugs called macrolones disrupt bacterial cell function to fight infectious diseases. Their experiments demonstrate that macrolones can work two different ways—either by interfering with protein production or corrupting DNA structure. 

Lab manager academy logo

Get training in Lab Crisis Preparation and earn CEUs.

One of over 25 IACET-accredited courses in the Academy.

Certification logo

Lab Crisis Preparation course

Because bacteria would need to implement defenses to both attacks simultaneously, the researchers calculated that drug resistance is nearly impossible. 

“The beauty of this antibiotic is that it kills through two different targets in bacteria,” said Alexander Mankin, distinguished professor of pharmaceutical sciences at 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.” 

Macrolones are synthetic antibiotics that combine the structures of two widely used antibiotics with different mechanisms. Macrolides, such as erythromycin, block the ribosome, the protein manufacturing factories of the cell. Fluoroquinolones, such as ciprofloxacin, target a bacteria-specific enzyme called DNA gyrase.

Two UIC laboratories led by Yury Polikanov, associate professor of biological sciences, and Mankin and Nora Vázquez-Laslop, research professor of pharmacy, examined the cellular activity of different macrolone drugs.  

Polikanov’s group, which specializes in structural biology, studied how these drugs interact with the ribosome, finding that they bind more tightly than traditional macrolides. The macrolones were even capable of binding and blocking ribosomes from macrolide-resistant bacterial strains and failed to trigger the activation of resistance genes. 

Interested in life sciences?

Subscribe to our free Life Sciences Newsletter.

Is the form not loading? If you use an ad blocker or browser privacy features, try turning them off and refresh the page.

Other experiments tested whether the macrolone drugs preferentially inhibited the ribosome or the DNA gyrase enzymes at various doses. While many designs were better at blocking one target or another, one that interfered with both at its lowest effective dose stood out as the most promising candidate. 

“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,” Polikanov said.  

The study also reflects the interdisciplinary collaboration at the UIC Molecular Biology Research Building, where researchers from the colleges of medicine, pharmacy, and liberal arts and sciences share neighboring laboratories and drive basic science discoveries like this one, the authors said. 

“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.” 

- This press release was originally published on the University of Illinois Chicago website and has been edited for style and clarity

Loading Next Article...
Loading Next Article...

CURRENT ISSUE - December 2024

2025 Industry and Equipment Trends

Purchasing trends survey results

Lab Manager December 2024 Cover Image