title: Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides.
abstract: Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC(50)], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Niels Møller
authors.initials: NM
authors.lastname: Andersen
authors.forename: Jacob
authors.initials: J
authors.lastname: Poehlsgaard
authors.forename: Ralf
authors.initials: R
authors.lastname: Warrass
authors.forename: Stephen
authors.initials: S
authors.lastname: Douthwaite
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D016978:Mannheimia haemolytica / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009154:Mutation; D009711:Nucleotides / Q000235:genetics; D016979:Pasteurella multocida / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects*; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects*; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015645:Tylosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D019155:Veterinary Drugs / Q000737:chemistry* / Q000494:pharmacology; D018942:Macrolides
chemical_list: D000900:Anti-Bacterial Agents; D004187:Disaccharides; D006571:Heterocyclic Compounds; D009711:Nucleotides; D012335:RNA, Ribosomal; D015645:Tylosin; D019155:Veterinary Drugs; C576258:20,23-dipiperidinyl-mycaminosyl-tylonolide; C485204:tulathromycin; D018942:Macrolides; C052319:tilmicosin