Inhibition of bacterial ribosome assembly: a suitable drug target?
The assembly of bacterial ribosomes is viewed with increasing interest as a potential target for new antibiotics. The in vivo synthesis and assembly of ribosomes are briefly reviewed here, highlighting the many ways in which assembly can be perturbed. The process is compared with the model in vitro process from which much of our knowledge is derived. The coordinate synthesis of the ribosomal components is essential for their ordered and efficient assembly; antibiotics interfere with this coordination and therefore affect assembly. It has also been claimed that the binding of antibiotics to nascent ribosomes prevents their assembly. These two contrasting models of antibiotic action are compared and evaluated. Finally, the suitability and tractability of assembly as a drug target are assessed.
Maguire
Bruce A
BA
Department of Exploratory Medicinal Sciences, Pfizer Global Research and Development, MS 8118W-106, Groton Laboratories, Groton, CT 06340, USA. bruce.maguire@pfizer.com
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011500:Protein Synthesis Inhibitors; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins