Bacterial ribosomal subunit synthesis: a novel antibiotic target
- PMID: 12455231
- DOI: 10.2174/1568005013343281
Bacterial ribosomal subunit synthesis: a novel antibiotic target
Abstract
The continuing increase in antibiotic-resistant pathogenic bacterial has stimulated research on the development of new antimicrobial agents and the identification of new cellular targets. One such target is the sequence of assembly steps required for the formation of bacterial ribosomal subunits. A large number of different protein synthesis inhibitors which affect large subunit function also prevent the 50S particle from being formed in growing cells. These compounds include the macrolide and ketolide antibiotics as well as certain lincosamides, B-type streptogramins and several other structurally unrelated translational inhibitors. This review describes the activities of these compounds as inhibitors of 50S subunit formation. For most of these drugs, their inhibitory effect on particle synthesis is equivalent to their effect on translation. This new target is thus of equal importance to translational inhibition as a mechanism of action of these compounds. Features of the 50S subunit precursor particle as a target for these drugs are described. Finally a model is presented which accounts for this activity and predicts certain features of the substrate for erythromycin methylase activity in inducible cells. Antibiotics which target subunit formation preferentially are predicted to be important bactericidal agents.
Similar articles
-
Preferential inhibition of protein synthesis by ketolide antibiotics in Haemophilus influenzae cells.Curr Microbiol. 2003 Feb;46(2):103-8. doi: 10.1007/s00284-002-3802-x. Curr Microbiol. 2003. PMID: 12520364
-
Structure-activity relationships for six ketolide antibiotics.Curr Microbiol. 2001 Mar;42(3):203-10. doi: 10.1007/pl00021055. Curr Microbiol. 2001. PMID: 11270656
-
Specific inhibition of 50S ribosomal subunit formation in Staphylococcus aureus cells by 16-membered macrolide, lincosamide, and streptogramin B antibiotics.Curr Microbiol. 2000 Aug;41(2):126-35. doi: 10.1007/s002840010106. Curr Microbiol. 2000. PMID: 10856379
-
The other target for ribosomal antibiotics: inhibition of bacterial ribosomal subunit formation.Infect Disord Drug Targets. 2006 Dec;6(4):377-90. doi: 10.2174/187152606779025842. Infect Disord Drug Targets. 2006. PMID: 17168803 Review.
-
The emerging new generation of antibiotic: ketolides.Curr Drug Targets Infect Disord. 2001 Aug;1(2):125-31. doi: 10.2174/1568005014606071. Curr Drug Targets Infect Disord. 2001. PMID: 12455409 Review.
Cited by
-
Dependency map of proteins in the small ribosomal subunit.PLoS Comput Biol. 2006 Feb;2(2):e10. doi: 10.1371/journal.pcbi.0020010. Epub 2006 Feb 17. PLoS Comput Biol. 2006. PMID: 16485038 Free PMC article.
-
Regulation of ribosomal protein genes: An ordered anarchy.Wiley Interdiscip Rev RNA. 2021 May;12(3):e1632. doi: 10.1002/wrna.1632. Epub 2020 Oct 10. Wiley Interdiscip Rev RNA. 2021. PMID: 33038057 Free PMC article. Review.
-
Ribosomal alterations contribute to bacterial resistance against the dipeptide antibiotic TAN 1057.Antimicrob Agents Chemother. 2004 Feb;48(2):619-22. doi: 10.1128/AAC.48.2.619-622.2004. Antimicrob Agents Chemother. 2004. PMID: 14742220 Free PMC article.
-
Screening of biomarkers of drug resistance or virulence in ESCAPE pathogens by MALDI-TOF mass spectrometry.Sci Rep. 2019 Dec 12;9(1):18945. doi: 10.1038/s41598-019-55430-1. Sci Rep. 2019. PMID: 31831867 Free PMC article.
-
The Mechanisms of Action of Ribosome-Targeting Peptide Antibiotics.Front Mol Biosci. 2018 May 14;5:48. doi: 10.3389/fmolb.2018.00048. eCollection 2018. Front Mol Biosci. 2018. PMID: 29868608 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources