Inhibition of bacterial isoprenoid synthesis by fosmidomycin, a phosphonic acid-containing antibiotic. 1989

Y Shigi
Fujisawa Pharmaceutical Co., Ltd., Tsukuba Research Laboratories, Ibaraki, Japan.

The mechanism of action of fosmidomycin (FR-31564), a phosphonic acid containing antibiotic, was examined against Escherichia coli, Micrococcus luteus and other bacteria. It converted growing Esch. coli cells into spheroplasts or swollen cells, but did not inhibit the enzymatic reactions of cell wall synthesis in ether-treated cells. Unlike bicyclomycin, phenethyl alcohol and mitomycin C, it did not reduce the amount of envelope lipoprotein, phospholipids, or DNA, but did reduce the amount of menaquinones and ubiquinones in growing Esch. coli cells. It also inhibited the biosynthesis of both carotenoids and menaquinones in M. luteus cells, suggesting that inhibition of the biosynthesis of a common precursor of these isoprenoids (possibly farnesyl pyrophosphate) might be the main site of its antibacterial activity.

UI MeSH Term Description Entries
D008074 Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes. Circulating Lipoproteins,Lipoprotein,Lipoproteins, Circulating
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D008837 Micrococcus A genus of gram-positive, spherical bacteria found in soils and fresh water, and frequently on the skin of man and other animals.
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D011809 Quinones Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D002338 Carotenoids The general name for a group of fat-soluble pigments found in green, yellow, and leafy vegetables, and yellow fruits. They are aliphatic hydrocarbons containing 4 terpene subunits. Carotenes,Carotenoid,Tetraterpene Derivatives,Tetraterpenes,Carotene,Derivatives, Tetraterpene
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D005578 Fosfomycin An antibiotic produced by Streptomyces fradiae. Phosphonomycin,Fosfomycin Trometamol Salt,Fosfomycin Tromethamine,Monuril,Phosphomycin,Tromethamine, Fosfomycin
D013104 Spheroplasts Cells, usually bacteria or yeast, which have partially lost their cell wall, lost their characteristic shape and become round. Spheroplast

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