Aminoglycosides

• What are some mechanisms of aminoglycoside resistance?

  Reduced uptake

  Decreased cell permeability

  Alterations at ribosomal binding site

  Production of aminoglycoside modifying enzymes
• What are some examples of aminoglycoside modifying enzymes (AMEs)?

  N-acetyltransferase

  O-nucleotidyltransferase

  O-phosphotransferase
• How does N-acetyltransferase lead to resistance in amionoglycosides?

  Acetylate an amino group (NH2) using acetyl coenzyme A -> modified drug fails to bind to target
• How does O-phosphotransferase lead to resistance in aminoglycosides?

  Transfer of phosphoryl group from ATP to a hydroxyl group (-OH) to the antibiotic -> modifed drug fails to bind to target
• How does O-nucleotidyltransferase lead to resistance in aminoglycosides?

  Transfer of adenyl group from ATP to a hydroxyl group (-OH) of the antibiotic -> modified drug fails to bind to target
• Give 5 aminoglycoside antibiotics.

  Gentamicin

  Tobramycin

  Amikacin

  Kanamyvin

  Streptomycin
• How do aminoglycosides work (brief)?

  Bind to aminoacyl site of 16S ribosomal RNA within the 30S ribosomal subunit -> codon misreading & mistranslation of proteins -> production of incorrect polypetides -> damages cell membrane
• What do aminoglycosides end in?

  -mycin

  -micin

  -cin