Aminoglycoside
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar).
[8] These activities are attributed to a primary mode of action as protein synthesis inhibitors, though additional mechanisms are implicated for some specific agents, and/or thorough mechanistic descriptions are as yet unavailable.
[2][3][8] The inhibition of protein synthesis is mediated through aminoglycosides' energy-dependent, sometimes irreversible binding, to the cytosolic, membrane-associated bacterial ribosome (image at right).
[8]) While specific steps in protein synthesis affected may vary somewhat between specific aminoglycoside agents, as can their affinity and degree of binding,[8] aminoglycoside presence in the cytosol generally disturbs peptide elongation at the 30S ribosomal subunit, giving rise to inaccurate mRNA translation and therefore biosynthesis of proteins that are truncated, or bear altered amino acid compositions at particular points.
Recent single-molecule tracking experiments in live E. coli showed an ongoing but slower protein synthesis upon treatment with different aminoglycoside drugs.
[9] (Spectinomycin, a related but distinct chemical structure class often discussed with aminoglycosides, does not induce mRNA misreading and is generally not bactericidal.
This is due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels drop, and allows a prolonged dosage interval.
Aminoglycosides can cause the cell to overcome the stop codons, insert a random amino acid, and express a full-length protein.
In approximately 10% of CF cases, the mutation in this gene causes its early termination during translation, leading to the formation of a truncated and non-functional CFTR protein.
It is believed that gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination codon, causing the ribosome to "skip" over the stop sequence and to continue with the normal elongation and production of the CFTR protein.
[15] The recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reevaluate the use of these antibacterial agents.
[16] This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity.
Current evidence shows that aminoglycosides do retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world.
