2016/12/13 by Zohar Eyal, Donna Matzov, Miri Krupkin +6 · 1 citation
Veterinary · Immunology and Microbiology · Medicine · #Veterinary medicine and infectious diseases #Toxin Mechanisms and Immunotoxins #Clostridium difficile and Clostridium perfringens research
paper · pdf · doi:10.1038/srep39004
openalex publication_date 2016/12/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The increasing appearance of pathogenic bacteria with antibiotic resistance is a global threat. Consequently, clinically available potent antibiotics that are active against multidrug resistant pathogens are becoming exceedingly scarce. Ribosomes are a main target for antibiotics, and hence are an objective for novel drug development. Lefamulin, a semi-synthetic pleuromutilin compound highly active against multi-resistant pathogens, is a promising antibiotic currently in phase III trials for the treatment of community-acquired bacterial pneumonia in adults. The crystal structure of the Staphylococcus aureus large ribosomal subunit in complex with lefamulin reveals its protein synthesis inhibition mechanism and the rationale for its potency. In addition, analysis of the bacterial and eukaryotes ribosome structures around the pleuromutilin binding pocket has elucidated the key for the drug's selectivity.