Gentamicin uptake in Staphylococcus aureus possessing plasmid-encoded, aminoglycoside-modifying enzymes

Area of Science:

• Microbiology
• Molecular Biology
• Pharmacology

Background:

• Gentamicin resistance in Staphylococcus aureus is often mediated by plasmid-encoded enzymes.
• Understanding the mechanism of gentamicin resistance is crucial for effective antibiotic therapy.

Purpose of the Study:

• To investigate the kinetics of gentamicin uptake in gentamicin-resistant and susceptible Staphylococcus aureus strains.
• To compare gentamicin uptake mechanisms in S. aureus with those of streptomycin in E. coli.

Main Methods:

• Utilized radiolabeled [3H]gentamicin to quantify uptake in resistant and susceptible S. aureus strains.
• Employed varying gentamicin concentrations and a membrane H+-ATPase inhibitor (N,N'-dicyclohexyl carbodiimide) to assess uptake dynamics.
• Compared experimental findings with previously published data on streptomycin uptake in E. coli.

Main Results:

• Gentamicin uptake was impaired in resistant strains at low concentrations (<2.0 µg/ml), with no observed killing.
• At higher concentrations (2.5–10.0 µg/ml), resistant strains exhibited rapid gentamicin uptake comparable to susceptible strains, leading to growth inhibition but not loss of viability.
• Inhibition of membrane H+-ATPase restored gentamicin uptake in resistant strains at low concentrations without affecting viability.

Conclusions:

• Gentamicin uptake in S. aureus differs from streptomycin uptake in E. coli, particularly in resistant strains with plasmid-encoded modifying enzymes.
• For 2-deoxystreptamine antibiotics like gentamicin, ribosomal binding can lead to accelerated uptake and growth inhibition without necessarily causing cell death in resistant S. aureus.