The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance.
Summary of "The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance."
The continued ability to treat bacterial infections requires effective antibiotics. The development of new therapeutics is guided by knowledge of the mechanisms of action of and resistance to these antibiotics. Continued efforts to understand and counteract antibiotic resistance mechanisms at a molecular level have the potential to direct development of new therapeutic strategies in addition to providing insight into the underlying biochemical functions impacted by antibiotics. The interaction of antibiotics with the peptidyltransferase center and adjacent exit tunnel within the bacterial ribosome is the predominant mechanism by which antibiotics impede translation, thus stalling growth. Resistance enzymes catalyze the chemical modification of the RNA that composes these functional regions, leading to diminished binding of antibiotics. This review discusses recent advances in the elucidation of chemical mechanisms underlying resistance and driving the development of new antibiotics.
Affiliation
Department of Cellular and Molecular Pharmacology and ‡Department of Pharmaceutical Chemistry, University of California, San Francisco , 600 16th St, MC2280, San Francisco, California 94158, United States.
Journal Details
This article was published in the following journal.
Name: ACS chemical biology
ISSN: 1554-8937
Pages: 64-72
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22208312
- DOI: http://dx.doi.org/10.1021/cb200418f
Medical and Biotech [MESH] Definitions
Beta-lactam Resistance
Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.
Drug Resistance, Fungal
The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation.
Drug Resistance, Bacterial
The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
Drug Resistance, Microbial
The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
Chloramphenicol O-acetyltransferase
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
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