title: Blast from the Past: Reassessing Forgotten Translation Inhibitors, Antibiotic Selectivity, and Resistance Mechanisms to Aid Drug Development.
abstract: Protein synthesis is a major target within the bacterial cell for antibiotics. Investigations into ribosome-targeting antibiotics have provided much needed functional and structural insight into their mechanism of action. However, the increasing prevalence of multi-drug-resistant bacteria has limited the utility of our current arsenal of clinically relevant antibiotics, highlighting the need for the development of new classes. Recent structural studies have characterized a number of antibiotics discovered decades ago that have unique chemical scaffolds and/or utilize novel modes of action to interact with the ribosome and inhibit translation. Additionally, structures of eukaryotic cytoplasmic and mitochondrial ribosomes have provided further structural insight into the basis for specificity and toxicity of antibiotics. Together with our increased understanding of bacterial resistance mechanisms, revisiting our treasure trove of "forgotten" antibiotics could pave the way for the next generation of antimicrobial agents.
authors.affiliation: Gene Center and Department of Biochemistry, Feodor-Lynenstr. 25, University of Munich, 81377 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Arenz
authors.affiliation: Gene Center and Department of Biochemistry, Feodor-Lynenstr. 25, University of Munich, 81377 Munich, Germany; Center for integrated Protein Science Munich, Feodor-Lynenstr. 25, University of Munich, 81377 Munich, Germany. Electronic address: Wilson@lmb.uni-muenchen.de.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000187:drug effects*; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011500:Protein Synthesis Inhibitors