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In a groundbreaking study from the University of Illinois Chicago, researchers have developed a new antibiotic that targets bacteria in two different ways, making it nearly impossible for bacteria to develop resistance. This innovative approach could revolutionize the fight against infectious diseases.
Published in the prestigious journal Nature Chemical Biology, the study explores how a novel class of synthetic drugs known as macrolones disrupts bacterial cell function. The experiments revealed that macrolones work by either interfering with protein production or corrupting DNA structure.
“Because bacteria would need to implement defenses to both attacks simultaneously, drug resistance becomes nearly impossible,” explained Alexander Mankin, a distinguished professor of pharmaceutical sciences at UIC.
Macrolones are unique synthetic antibiotics combining the structures of two well-known antibiotics with distinct mechanisms. Macrolides, like erythromycin, block ribosomes, the cell’s protein factories, while fluoroquinolones, such as ciprofloxacin, target a bacteria-specific enzyme called DNA gyrase.
UIC’s two leading laboratories, headed by Yury Polikanov, an associate professor of biological sciences, and Mankin and Nora Vázquez-Laslop, a research professor of pharmacy, investigated the cellular activity of various macrolone drugs.
Polikanov’s team, specializing in structural biology, discovered that these drugs bind more tightly to ribosomes than traditional macrolides. Remarkably, macrolones could bind and block ribosomes in macrolide-resistant bacterial strains without activating resistance genes.
Further experiments assessed whether macrolone drugs inhibited ribosomes or DNA gyrase enzymes at different doses. One particular design stood out, effectively targeting both at the lowest effective dose, presenting the most promising candidate.
“By hitting two targets at the same concentration, you make it almost impossible for bacteria to develop a simple genetic defense,” Polikanov noted.
The study highlights the interdisciplinary collaboration at UIC’s Molecular Biology Research Building, where researchers from the colleges of medicine, pharmacy, and liberal arts and sciences work together, fostering significant scientific discoveries.
“The main outcome of this work is understanding how to move forward,” Mankin stated. “We are providing chemists with the knowledge needed to optimize these macrolones to target both sites.”
In addition to Mankin, Polikanov, and Vázquez-Laslop, co-authors of the paper include Elena Aleksandrova, Dorota Klepacki, and Faezeh Alizadeh from UIC.
This dual-action antibiotic represents a significant step forward in combating bacterial resistance, potentially transforming the landscape of infectious disease treatment and offering new hope in the battle against resistant bacteria.
