Ribosome-targeting Antibiotics

Hummel, H., Bock, A., 23S ribosomal RNA mutations in halobacteria conferring resistance to the anti-80S ribosome targeted antibiotic anisomydn. Nuddc Acids Res. 1987, 15, 2431-2443. 

Tetracycline occupies a pocket formed by helices 31 and 34 of 16S rRNA (1 l)As with most ribosome targeting antibiotics, the con-... 

Plasmid- ortransposon-encoded chloramphenicol acetyltransferases (CATs) are responsible for resistance by inactivating the antibiotic. CATs convert chloramphenicol to an acetoxy derivative which fails to bind to the ribosomal target. Several CATs have been characterized and found to differ in properties such as elecfrophorefic mobilify and cafalyfic acfivify. 

In both bacteria and eucarya the susceptibility to certain ribosome-targeted inhibitors correlates with specific primary structural features of rR24A, or with features of the ribosomal domain that acts as the antibiotic binding sites. Firstly, resistance to specific ribosome-directed drugs is conferred by single-base changes within phylogenetically... 

Macrolides are a group of antibiotics, produced in nature by many actinomycetes strains, that are composed of a 12- to 16-membered lactone ring, to which one or more sugar substituents is attached. They target the peptidyl transferase center on the 50S ribosomal subunit and function primarily by interfering with movement of the nascent peptide away from the active site and into the exit tunnel. 

The ribosome is the cellular target of a large and chemically diverse group of antibiotics. The antibiotic binding sites are clustered at functional centers of the ribosome and the majority are composed exclusively of RNA. The drugs interfere with the positioning and movement of substrates, products and ribosomal components that are essential for protein synthesis. 

Transcriptional inhibitors could be used simultaneously. Rifampicin blocks chloroplast and mitocondrian RNA synthesis [23, 24], while tagetitoxin is a very specific inhibitor of chloroplast RNA polymerase [25]. Treatment with these antibiotics does not inhibit Rubisco SSU synthesis since the promoter is part of the nuclear genome, while the cytosolic ribosomes are not affected by streptomycin. Therefore SSU promoters can be used to drive transgene expression and facilitate the accumulation of recombinant proteins. Expressed proteins are targeted to a suitable cellular compartment, such as the cytoplasm, apoplastic space or chloroplast, depending on the nature of the protein. 

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