Biologists have discovered how bacteria develop resistance to antibiotics.

Bacterial resistance to antibiotics is one of the most pressing issues in medicine. Misuse or overuse of antibacterial drugs has already made it difficult (and sometimes impossible) to treat diseases such as tuberculosis, pneumonia, gonorrhea, and bloodstream infections. If the situation does not improve, many common infections and minor injuries could once again become deadly.

Among the various mechanisms that bacteria employ to defend against antibiotics, plasmids play a crucial role. These small "extra" circular DNA molecules can live independently within a bacterial cell and carry genes responsible for antibiotic resistance. Studying them directly helps scientists develop strategies aimed at "switching off" or eliminating resistance genes.

Recently, an international research team led by Thomas C. McLean from the John Innes Centre (UK) studied the model plasmid RK2, which is frequently used in antibiotic resistance research. The scientists focused on the KorB protein, as it is essential for the plasmid's maintenance within the bacteria. Previously, this protein had been implicated in gene regulation, but its precise mechanism of action remained a mystery.

By employing modern microscopy and X-ray crystallography techniques, the researchers discovered that KorB interacts closely with the KorA protein. Together, they function like a "clamp" and "lock": KorB can slide along the bacterial DNA, while KorA "locks" KorB at specific moments (and locations).

This results in a remote blocking (long-range switching off) of the genes located in the plasmid, allowing it to "adjust" the conditions within the bacteria to its own needs and protect itself, thus increasing the overall level of the bacteria's resistance to antibiotics. The research findings have been published in the journal Nature Microbiology.

The results pave the way for the development of new drugs capable of "destabilizing" plasmids in bacteria and restoring their sensitivity to antibiotics. The team plans to expand their research to investigate how the mechanism they discovered operates in other, more clinically significant plasmids.