High-resolution landscape of an antibiotic binding site. (https://www.nature.com/articles/s41586-023-06495-6)

These scientists wanted to learn more about how antibiotics work and how bacteria can become resistant to them. They focused on a specific antibiotic called rifampicin and a part of the bacteria called RNA polymerase, which is an important enzyme.

To study this, the scientists used a special technique called multiplex genome engineering. This allowed them to make changes to the DNA of the bacteria and create many different versions of the RNA polymerase enzyme. They made a total of 760 different changes to the enzyme.

By studying how the antibiotic and the enzyme interacted with each other, the scientists discovered that there was a specific part of the enzyme, called an alpha helix, where changes could make the antibiotic work much better or stop it from working at all. Some changes even made the antibiotic more powerful and able to kill the bacteria instead of just stopping their growth.

The scientists also found that these changes in the enzyme caused problems when the bacteria tried to copy their DNA. This led to breaks in the DNA, which were harmful to the bacteria. They also found other changes that made the enzyme work faster, which affected how the bacteria made new molecules.

In addition to studying the bacteria in the lab, the scientists also looked at bacteria found in nature. They discovered that some of the changes they made to the enzyme also occurred naturally in bacteria. This means that bacteria can naturally develop ways to resist antibiotics or change how they work.

Overall, this study helped the scientists understand more about how antibiotics work, how bacteria can become resistant to them, and how changes in the bacteria's DNA can affect their survival.

Yang KB., Cameranesi M., Gowder M., Martinez C., Shamovsky Y., Epshtein V., Hao Z., Nguyen T., Nirenstein E., Shamovsky I., Rasouly A., Nudler E. High-resolution landscape of an antibiotic binding site. Nature. 2023 Oct;622(7981):180-187. doi: 10.1038/s41586-023-06495-6. Epub 2023 Aug 30.