News Excerpt:

For a new paper in Nature Chemical Biology, researchers examined how a class of synthetic drugs called macrolones disrupt bacterial cell function to fight infectious diseases.

What are Macrolones:

• 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.

Key Points:

• Dual-action mechanism: Macrolones work by targeting two different cellular processes in bacteria: 
• Interfering with protein production
• Corrupting DNA structure
• Drastically reduced resistance: This dual-action approach makes it approximately 100 million times more difficult for bacteria to develop resistance. The bacteria would need to simultaneously evolve defenses against both mechanisms, which is highly improbable.
• Key findings of the research: 
• Macrolones bind more tightly to ribosomes than traditional macrolides. 
• They can even bind to and block ribosomes from macrolide-resistant bacterial strains. 
• Macrolones do not trigger the activation of resistance genes. 
• Some macrolone designs were found to inhibit both ribosome and DNA gyrase enzymes at the same concentration, making them particularly promising.

Implications for future antibiotic development: 

• The research suggests that optimizing macrolones to target both cellular processes simultaneously could lead to more effective antibiotics with a significantly lower risk of resistance development.

Significance of the research:

• The significance of this research lies in its potential to address the growing global concern of antibiotic resistance.
• As antibiotic resistance continues to be a major threat to global health, this research provides a promising new direction for the development of more effective and lasting antibiotic treatments.