Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria

• DOI: 10.7554/elife.62655
• Publication Date: 2020-10-08T17:00:25Z
• Authors: Kyle Mangano; Tanja Florin; Xinhao Shao; Dorota Klepacki; Irina Chelysheva; Zoya Ignatova; Yu Gao; Alexander S Mankin; Nora Vázquez-Laslop
• Keywords: 0301 basic medicine; QH301-705.5; Science; antibiotics; 03 medical and health sciences; Biochemistry and Chemical Biology; Escherichia coli; Biology (General); Uncategorized; ribosome profiling; 0303 health sciences; antibacterial peptides; Q; R; Peptide Chain Termination, Translational; 3. Good health; rescue sysytems; ribosome; Codon, Terminator; Medicine; PrAMPs; Ribosomes; Genome, Bacterial; Antimicrobial Cationic Peptides

Biochemical studies suggested that the antimicrobial peptide apidaecin (Api) inhibits protein synthesis by binding in the nascent peptide exit tunnel and trapping the release factor associated with a terminating ribosome. The mode of Api action in bacterial cells had remained unknown. Here genome-wide analysis reveals that in bacteria, Api arrests translating ribosomes at stop codons and causes pronounced queuing of the trailing ribosomes. By sequestering the available release factors, Api promotes pervasive stop codon bypass, leading to the expression of proteins with C-terminal extensions. Api-mediated translation arrest leads to the futile activation of the ribosome rescue systems. Understanding the unique mechanism of Api action in living cells may facilitate the development of new medicines and research tools for genome exploration.