A new antibiotic that works in two ways could make it extremely difficult for bacteria to develop resistance. Researchers from the University of Illinois Chicago found that a class of synthetic drugs called macrolones can disrupt bacterial cell function by either interfering with protein production or corrupting DNA structure.
Macrolones are created by combining the structures of two widely used antibiotics with different mechanisms. They work in two ways: either by blocking the ribosome, the protein manufacturing factories of the cell, or by targeting a bacteria-specific enzyme called DNA gyrase.
The researchers studied how these drugs interact with the ribosome and found that they bind more tightly than traditional macrolides. The macrolones were even capable of binding and blocking ribosomes from macrolide-resistant bacterial strains.
One design stood out as the most promising candidate, which interfered with both the ribosome and DNA gyrase enzymes at its lowest effective dose. This means that bacteria would need to implement defenses to both attacks simultaneously, making it nearly impossible for them to develop resistance.
The study highlights the importance of interdisciplinary collaboration and provides insights into how chemists can optimize macrolones to hit both targets.
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Source: https://phys.org/news/2024-07-dual-action-antibiotic-bacterial-resistance.html