A Serendipitous Discovery Could Hold the Key to Solving Antibiotic Resistance

An international research team has achieved a major breakthrough in understanding how bacteria develop antibiotic resistance, a growing global public health concern. This discovery highlights the complex roles of plasmids—small DNA molecules within bacteria that carry genes responsible for resistance. By unraveling these mechanisms, scientists can develop innovative treatments to combat drug-resistant infections more effectively.

Unveiling the KorB-KorA Interaction

Researchers at the John Innes Centre, collaborating with experts from Madrid, New York, and Birmingham, used the model plasmid RK2, a global reference for studying antibiotic resistance. Their work focused on KorB, a DNA-binding protein essential for plasmid survival within bacterial hosts. While KorB was known to regulate gene expression, the exact mechanism remained unclear.

Through advanced microscopy and protein crystallography, the team discovered that KorB interacts with another molecule, KorA, to form a regulatory system. This KorB-KorA complex functions as a gene-silencing mechanism: KorB acts as a DNA sliding clamp, while KorA locks it in place to shut down gene expression. This process ensures the plasmid remains stable and undetected within its bacterial host.

Transforming Curiosity into Discovery

Dr. Thomas McLean, the study’s first author, highlighted how a curiosity-driven experiment led to a breakthrough. “We initially focused on KorB, but a Friday afternoon experiment revealed KorA’s role in clamping KorB at the right time and place, redirecting our research on long-range gene regulation in bacteria.”

This discovery sheds light on how the KorB-KorA complex silences distant genes, enabling plasmids to persist in bacterial hosts. The findings open the door to therapies that destabilize plasmids and re-sensitize bacteria to antibiotics.

The study resolves a decades-long mystery of how KorB regulates genes in the multi-drug-resistant plasmid RK2. Researchers are now expanding their work to other clinically significant plasmids and further investigating the KorB-KorA mechanism.

Published in Nature Microbiology, the study offers new hope for combating antibiotic resistance.

Read Original Article: Scitechdaily

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