The Macrolides are a family of antibiotics whose structures contain large lactone rings linked through glycoside bonds with amino sugars. The most important members of the group are erythromycin and oleandomycin. Erythromycin is active against most Gram-positive bacteria, Neisseria, Legionella and Haemophilus, but not against the Enterobacteriaceae. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. Binding inhibits elongation of the protein by peptidyl transferase or prevents translocation of the ribosome or both. Macrolides are bacteriostatic for most bacteria but are cidal for a few Gram-positive bacteria.
Chloramphenicol is entirely selective for 70S ribosomes and does not affect 80S ribosomes. Its unfortunate toxicity towards the small proportion of patients who receive it is in no way related to its effect on bacterial protein synthesis. However, since mitochondria probably originated from procaryotic cells and have 70S ribosomes, they are subject to inhibition by some of the protein synthesis inhibitors including chloroamphenicol. This likely explains the toxicity of chloramphenicol. The eukaryotic cells most likely to be inhibited by chloramphenicol are those undergoing rapid multiplication, thereby rapidly synthesizing mitochondria. Such cells include the blood forming cells of the bone marrow, the inhibition of which could present as aplastic anemia. Chloramphenicol was once a highly prescribed antibiotic and a number of deaths from anemia occurred before its use was curtailed. Now it is seldom used in human medicine except in life-threatening situations (e.g. typhoid fever).
Tetracycline antibiotics are bacteriostatic agents and work by inhibiting the bacterial protein synthesis via interaction with the 30S subunit of the bacterial ribosome. Tetracyclines are effective against a wide variety of microorganisms, including spirochetes, atypical bacteria, rickettsia, and amebic parasites.
Many of the most effective antibiotics used in medicine today are small molecules produced by fungi. The properties of an antibiotic are sometimes determined by its activity on the different regions on the bacterial ribosome. These molecules are effective by inhibiting bacterial protein synthesis. The antibiotic Anisomycin is an effective inhibitor of fungal and protozoal growth. Anisomycin uses an effective blocking protein that works by shutting down the peptidyl transferase reaction within ribosomes. The ribosomes of eucaryotic mitochondria (and chloroplasts) will often resemble those of bacteria in their sensitivity to inhibitors. Therefore, some antibiotics such as Anisomycin can have a deletrious effect on human mitochondria.
Protein synthesis inhibitors Many therapeutically useful antibiotics owe their action to inhibition of some step in the complex process of translation. Their attack is always at one of the events occurring on the ribosome and rather than the stage of amino acid activation or attachment to a particular tRNA. Most have an affinity or specificity for 70S (as opposed to 80S) ribosomes, and they achieve their selective toxicity in this manner. The most important antibiotics with this mode of action are the tetracyclines, chloramphenicol, the macrolides (e.g. erythromycin) and the aminoglycosides (e.g. streptomycin).
The tetracyclines consist of eight related antibiotics which are all natural products of , although some can now be produced semisynthetically. Tetracycline, chlortetracycline and doxycycline are the best known. The tetracyclines are broad-spectrum antibiotics with a wide range of activity against both Gram-positive and Gram-negative bacteria. The tetracyclines act by blocking the binding of aminoacyl tRNA to the A site on the ribosome. Tetracyclines inhibit protein synthesis on isolated 70S or 80S (eukaryotic) ribosomes, and in both cases, their effect is on the small ribosomal subunit. However, most bacteria possess an active transport system for tetracycline that will allow intracellular accumulation of the antibiotic at concentrations 50 times as great as that in the medium. This greatly enhances its antibacterial effectiveness and accounts for its specificity of action, since an effective concentration cannot be accumulated in animal cells. Thus a blood level of tetracycline which is harmless to animal tissues can halt protein synthesis in invading bacteria.
: Oxazolidinones are synthetic agents, the original members of which were MAO inhibitors (). One, linezolid, is now available in some countries for the treatment of resistant staphylococcal infection (). These drugs have a novel mechanism of action on ribosomal protein synthesis, and are active against strains resistant to other classes of antibiotics (). Linezolid can be given orally as well as parenterally.