Mechanism of Action of Aminoglycosides



NOTE- We recommend that you view Mechanism of Translation of mRNA by tRNA in Ribosomes prior to viewing the animations below so as to gain a better understanding of the topic.

Aminoglycosides literally means a molecule containing an amino group (amino-) and a sugar moiety (glycoside). These molecules are therefore produced naturally generally by bacteria of the genus Streptomyces and Micromonospora. It is a general observation that aminoglycosides obtained from Micromonospora genus of bacteria have nomenclature suffixed with the term -micin (such as Amikacin Gentamicin, Netilmicin, Sisomicin, Isepamicin, Verdamicin, Astromicin); while those from the Streptomyces genus have nomenclature suffixed with the term -mycin (such as Streptomycin, Neomycin, Kanamycin, Hygromycin B, Spectinomycin, Paromomycin). Aminoglycosides inhibit bacterial growth via 2 pathways:

  1. Interfering with Translation by causing a Misreading of the Codons along the mRNA
  2. Interfering with the translocation of tRNA from the A-Site to the P-Site

Interfering with Translation by causing a Misreading of the Codons along the mRNA

Aminoglycosides inhibit translation of the mRNA by binding to the 30S subunit of the ribosome. The irreversible binding of the aminoglycosides to the 30S subunit of the ribosome causes the misreading of the codons along the mRNA. This misreading of the codons causes an error in the proofreading process of translation leading to improper protein expression leading to bacterial cell death.

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The above animations has been supplied by Dr. Gary E. Kaiser from the Community College of Baltimore County- and it illustrates the mechanism of action of how translation of mRNA by tRNA occurs in ribosomes. The transcript of the animation is as follows:

“The aminoglycosides (streptomycin, neomycin, netilmicin, tobramycin, gentamicin, amikacin, etc.) bind irreversibly to the 30S subunit of bacterial ribosomes. Aminoglycosides interfere with the proofreading process that helps assure the accuracy of translation. Possibly the antibiotics reduce the rejection rate for tRNAs that are near matches for the codon. This leads to misreading of the codons or premature termination of protein synthesis.

Slide 1: Aminoglycosides bind irreversibly to the 30S ribosomal subunit. This can interfere with the proofreading process that helps assure the accuracy of translation. Possibly the antibiotics reduce the rejection rate of tRNA that are near matches for codons. This leads to misreading of the codons or premature termination of protein synthesis.

Slide 2: In this example, the codon CGC codes for the amino acid arginine. As a result of misreading, a near-match tRNA with the anticodon GAG pairs with the GCG codon. This tRNA, however, carries the amino acid leucine not arginine.

Slide 3: Translation continues

Slide 4: In this example, the codon GGA codes for the amino glycine. As a result of misreading, a near-match tRNA with the anticodon CAU pairs with the GGA codon. This tRNA, however, carries the amino acid histidine and not glycine.  ”

Interfering with the translocation of tRNA from the A-Site to the P-Site

Aminoglycosides inhibit translation of mRNA by binding irreversibly to the 30S subunit of the ribosomes and inhibiting the translocation of the tRNA from the A-site of the ribosome to the P-site of the ribosome. As a result of which the protein sequence does not get elongated to the full sequence, leading to incomplete protein expression. Since the protein is not fully expressed, the small peptide chains are not capable of functioning like the whole proteins, leading to faulty cellular function which eventually causes cell death of the bacteria.

Sorry, either Adobe flash is not installed or you do not have it enabled

The above animations has been supplied by Dr. Gary E. Kaiser from the Community College of Baltimore County- and it illustrates the mechanism of action of how translation of mRNA by tRNA occurs in ribosomes. The transcript of the animation is as follows:

”  The aminoglycosides (streptomycin, neomycin, netilmicin, tobramycin, gentamicin, amikacin, etc.) bind irreversibly to the 30S subunit of bacterial ribosomes. There is evidence that some prevent the transfer of the peptidyl tRNA from the A-site to the P-site, thus preventing the elongation of the polypeptide chain.  ”

References

  1. BD Davis. Mechanism of bactericidal action of aminoglycosides. Microbiology and Molecular Biology Reviews, 1987 – Am Soc Microbiol. 341-350.
  2. Feero, W. Gregory; Guttmacher, Alan E.; Dietz, Harry C. (2010). “New Therapeutic Approaches to Mendelian Disorders”. New England Journal of Medicine 363 (9): 852–863.

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