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The application of molecular techniques for the study of aminoglycoside resistance

K J Shaw1, F J Sabatelli, L Naples

  • 1Schering-Plough Research Institute, Kenilworth, NJ.

Methods in Molecular Medicine
|March 11, 2011
PubMed

Insights

Aminoglycosides are vital antibiotics despite toxicity, offering rapid bacterial killing. Resistance often arises from plasmid-borne genes encoding enzymes that inactivate these crucial antibacterial agents.

Area of Science:

  • Pharmacology
  • Microbiology
  • Infectious Diseases

Background:

  • Aminoglycosides have been clinically utilized since 1944.
  • Despite known nephrotoxicity and ototoxicity, they remain essential in hospitals for rapid bactericidal activity, particularly with beta-lactams.
  • Bacterial resistance is a growing concern, impacting treatment efficacy.

Purpose of the Study:

  • To review the mechanisms of bacterial resistance to aminoglycosides.
  • To highlight the clinical significance of aminoglycosides in antibacterial therapy.
  • To discuss the enzymes responsible for aminoglycoside inactivation.

Main Methods:

  • Literature review of aminoglycoside use and resistance mechanisms.
  • Analysis of factors contributing to clinical aminoglycoside resistance.
  • Categorization of aminoglycoside-inactivating enzymes.

Main Results:

  • Aminoglycoside resistance is primarily driven by modifying enzymes, altered cell permeability, or target modification.
  • Acquisition of plasmid-borne genes encoding modifying enzymes is a common cause of high-level resistance.
  • Three main classes of enzymes are identified as responsible for aminoglycoside inactivation.

Conclusions:

  • Aminoglycosides remain indispensable antibacterial agents due to their potent bactericidal effects.
  • Understanding resistance mechanisms, especially enzyme-mediated inactivation, is critical for effective clinical use.
  • Further research into combating aminoglycoside resistance is warranted to preserve their therapeutic value.

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