A multi-institutional collaboration led by researchers at Ben-Gurion University has determined the cryo-EM structure of an antibiotic-resistant bacterial ribosome at 3.1 Å resolution. The structure, published in Science, reveals precisely how a single point mutation in the 23S rRNA confers resistance to macrolide antibiotics, a clinically critical drug class.

The project involved research groups from BGU, Tel Aviv University, and the Hebrew University, with all cryo-EM data collected at the Ilse Katz Institute facility over a two-week campaign. More than 600,000 ribosome particles were picked and classified, ultimately yielding a consensus reconstruction with clearly resolved antibiotic binding site residues.

The structural insights from this work are already being used by the group to guide the rational design of next-generation antibiotics that can overcome the resistance mutation. A follow-up drug screening program is underway in collaboration with an Israeli pharmaceutical company.