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[Effect of fosfidomycin on development of various infections in mice]
V D Potapov1, I V Bakhteeva, V N Borzenkov
1SSC Applied Microbiology, Obolensk, Moscow Region.
Abstract:
Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.
Insights
Fosmidomycin, an antibiotic inhibiting isoprenoid biosynthesis, showed protective effects against tularemia, typhus, and coli-septicemia in mice. Its role in tuberculosis treatment and the involvement of free radicals in its therapeutic action require further investigation.
Area of Science:
- Microbiology and Pharmacology
- Biochemistry of Isoprenoid Biosynthesis
Context:
- Fosmidomycin is known as an inhibitor of the non-mevalonate pathway.
- It has been investigated as a potential antimalarial agent.
- Previous studies explored its therapeutic potential in various infections.
Purpose:
- To evaluate the protective effect of fosmidomycin against experimental bacterial infections in mice.
- To assess the efficacy of fosmidomycin in treating chronic tuberculosis in mice.
- To investigate the potential mechanism of action involving free radicals.
Summary:
- Fosmidomycin demonstrated a protective effect in mice infected with tularemia, typhus, and coli-septicemia.
- No positive effect was observed in mice with chronic tuberculosis at the tested dosage.
- Electron spin resonance (ESR) detected long-living nitroxil free radicals in fosmidomycin solutions under oxidative conditions, suggesting their potential role in its therapeutic effects.
Impact:
- Highlights fosmidomycin's potential as a broad-spectrum antibiotic against specific bacterial infections.
- Indicates limitations of fosmidomycin for chronic tuberculosis treatment.
- Suggests a novel mechanism of action for fosmidomycin involving free radical generation.