Amikacin Pathway

Amikacin is an aminoglycoside antibiotic that inhibits bacterial protein synthesis. Amikacin binds irreversibly to the bacterial 30S ribosomal subunit protein and 16S rRNA and prevents the formation of the initiation complex with messenger RNA. More specifically, amikacin binds four nucleotides of the 16S rRNA and a single amino acid of protein S12. This interferes with the decoding site in the vicinity of nucleotide 1400 in 16S rRNA of the 30S subunit. This region interacts with the wobble base of the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so that incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides, and the breakup of polysomes into nonfunctional monosomes.

Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

References

1. Amikacin (CPhA monograph). (2009). [Electronic version]. e-CPS. Retrieved July 17, 2009.
2. Song, K.S. (2004). Ribosomal protein synthesis inhibitors. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 827-833). Berlin, Germany: Springer.