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Plasmid-mediated fosfomycin resistance is due to enzymatic modification of the antibiotic
Antimicrobial Agents and Chemotherapy
|July 1, 1985
Abstract:
The molecular mechanism of plasmid-mediated resistance to fosfomycin is described. The antibiotic was inactivated intracellularly and remained inside the cells. Modification was also obtained from cell extracts and was not energy dependent. The modifying enzyme seems to have sulfhydryl groups in its active center.
Insights
Plasmid-mediated fosfomycin resistance involves intracellular inactivation of the antibiotic by a modifying enzyme. This enzyme, likely containing sulfhydryl groups, does not require cellular energy for its activity.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Fosfomycin is a broad-spectrum antibiotic.
- Plasmid-mediated resistance is a growing concern in infectious diseases.
- The specific mechanisms of fosfomycin resistance require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanism of plasmid-mediated fosfomycin resistance.
- To characterize the enzyme responsible for fosfomycin inactivation.
Main Methods:
- Analysis of fosfomycin inactivation within bacterial cells.
- Enzymatic modification assays using cell extracts.
- Determination of energy dependence of the modification reaction.
- Identification of key functional groups in the enzyme's active site.
Main Results:
- Fosfomycin was inactivated intracellularly, with the modified antibiotic remaining within the cells.
- A fosfomycin-modifying enzyme was identified in cell extracts.
- The modification process was independent of cellular energy.
- Evidence suggests the enzyme's active center contains sulfhydryl groups.
Conclusions:
- Plasmid-mediated fosfomycin resistance is achieved through intracellular enzymatic inactivation.
- The identified enzyme likely utilizes sulfhydryl groups for its catalytic activity.
- Understanding this mechanism is crucial for combating fosfomycin resistance.