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Aminoglycoside uptake increased by tet gene expression.
T L Merlin1, G E Davis, W L Anderson
1Laboratory Service, Albuquerque Veterans Administration Medical Center, New Mexico 87108.
Antimicrobial Agents and Chemotherapy
|September 1, 1989
Summary
The expression of tetracycline resistance (tet) genes enhances bacterial uptake of aminoglycoside antibiotics. This increased uptake leads to reduced bacterial growth and protein synthesis, highlighting a novel mechanism for antibiotic susceptibility.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Extrachromosomal tet genes confer tetracycline resistance in gram-negative bacteria.
- These genes also influence susceptibility to aminoglycoside antibiotics.
- The mechanism underlying this altered susceptibility requires investigation.
Purpose of the Study:
- To determine if tet gene expression increases aminoglycoside susceptibility by enhancing bacterial uptake.
- To elucidate the mechanism by which tet expression affects aminoglycoside uptake.
Main Methods:
- Utilized [3H]gentamicin uptake assays in Escherichia coli and Salmonella typhimurium strains.
- Compared uptake in bacterial strains with and without tet gene expression.
- Measured bacterial protein synthesis and growth rates.
- Assessed bacterial membrane potential.
Main Results:
- tet gene expression significantly accelerated energy-dependent [3H]gentamicin uptake.
- Increased aminoglycoside uptake correlated with decreased bacterial protein synthesis and growth.
- This effect was observed regardless of tet gene class (B or C), expression level (constitutive or induced), or location (plasmid or chromosome).
- No significant change in bacterial membrane potential was detected.
Conclusions:
- tet gene expression enhances aminoglycoside uptake in gram-negative bacteria.
- This enhanced uptake mechanism contributes to increased susceptibility to aminoglycoside antibiotics.
- The mechanism may involve increased carrier availability or a lowered threshold for membrane potential required for uptake.