Disease relevance of FOSFOMYCIN

• We now show that cells with inactivated murMN also have a third phenotype: an increased susceptibility to lysis when exposed to low concentrations of fosfomycin, d-cycloserine, vancomycin, and nisin, indicating a wide-spectrum hypersensitivity to inhibitors of both early and late stages of cell wall biosynthesis [1].
• Codon randomization and selection for the ability of resulting clones to confer fosfomycin resistance to Escherichia coli were used to identify residues critical for FosA function [2].
• Functional analysis of active site residues of the fosfomycin resistance enzyme FosA from Pseudomonas aeruginosa [2].
• Mutations of Cys115 to Asp exist in pathogens such as Mycobacteria or Chlamydia rendering these organisms resistant to fosfomycin [3].
• Here we report the cloning and characterization of a complete fosfomycin biosynthetic cluster from Streptomyces fradiae and heterologous production of fosfomycin in S. lividans [4].

Psychiatry related information on FOSFOMYCIN

• Increasing the dose infused (10 g) markedly shortened the latency period between reaching a sufficient concentration of fosfomycin in the CSF [5].

High impact information on FOSFOMYCIN

• The incorporation of the artificial cell-wall precursors was enhanced when incubated with fosfomycin, an inhibitor of cell-wall precursor biosynthesis [6].
• Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster [4].
• Penetration of fosfomycin into inflammatory lesions in patients with cellulitis or diabetic foot syndrome [7].
• Thus, the cyclization of HPP to fosfomycin clearly represents an intriguing conversion beyond the scope entailed by common biological epoxidation and C-O bond formation [8].
• We investigated the distribution of the broad-spectrum antibiotic fosfomycin in infected soft tissue of patients with uncomplicated cellulitis of the lower extremities or diabetic foot infection using in vivo microdialysis [7].

Chemical compound and disease context of FOSFOMYCIN

• In vitro synergism between daptomycin and fosfomycin against Enterococcus faecalis isolates with high-level gentamicin resistance [9].
• The potential clinical relevance of this was examined in mice colonized with E. coli O157:H7 and given either ciprofloxacin or fosfomycin [10].
• In vitro activity of fosfomycin, alone and in combination, against methicillin-resistant Staphylococcus aureus [11].
• The in vitro and in vivo activity of FR-31564 [sodium hydrogen 3-(N-hydroxyformamido)propylphosphate] against gram-positive and -negative aerobic and anaerobic bacteria was investigated and compared with that of fosfomycin, cephalexin, carbenicillin, and trimethoprim-sulfamethoxazole [12].
• The amount of active intracellular fosfomycin in these STEC isolates was 100- to 200-fold less than that in E. coli C600 harboring pREFTT47B408 in the presence of either L-alpha-glycerophosphate or glucose-6-phosphate [13].

Biological context of FOSFOMYCIN

• It provides an attractive template for the design of novel antibiotic drugs and is the target of the naturally occurring antibiotic fosfomycin, which covalently attaches to Cys115 in the active site of the enzyme [3].
• Both of these plasmids are present in parental S. marcescens strains resistant to fosfomycin [14].
• The pharmacokinetics of phosphomycin were studied in seven patients with pleural effusion of varied etiologies [15].
• Although the addition of the substrate, fosfomycin, has no appreciable effect on the association kinetics of enzyme and metal, it significantly decreases the dissociation rate, suggesting that the substrate interacts directly with the metal center [16].
• Nucleotide sequence and intracellular location of the product of the fosfomycin resistance gene from transposon Tn2921 [17].

Anatomical context of FOSFOMYCIN

• Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections [18].
• Distribution and antimicrobial activity of fosfomycin in the interstitial fluid of human soft tissues [18].
• Immunosuppressive activity of fosfomycin on human T-lymphocyte function in vitro [19].
• Immunomodulatory effect of fosfomycin on human B-lymphocyte function [20].
• Concentrations of fosfomycin in the cerebrospinal fluid of neurointensive care patients with ventriculostomy-associated ventriculitis [21].

Associations of FOSFOMYCIN with other chemical compounds

• In vitro susceptibility testing procedures for fosfomycin tromethamine [22].
• The in vitro activities of imipenem alone and in combination with teicoplanin, fosfomycin, and rifampin were tested against clinical isolates of enterococci and staphylococci [23].
• Kinetics, stoichiometry, and identification of the reactive thiolate in the inactivation of UDP-GlcNAc enolpyruvoyl transferase by the antibiotic fosfomycin [24].
• Of the rest of the antibiotics studied, amoxicillin-clavulanic acid, clindamycin, and fosfomycin displayed good in vitro activities [25].
• A randomized study was conducted to assess the clinical and microbiological efficacies of a single 3-g dose of fosfomycin trometamol for the treatment of uncomplicated lower urinary tract infections in women compared with a 5-day regimen of cephalexin at 0.5 g four times daily [26].

Gene context of FOSFOMYCIN

• Our results suggest that the fosfomycin resistance in these STEC isolates is due to concurrent effects of alteration of the glpT and/or uhp transport systems and of the enhanced transcription of the murA gene [13].
• Namely, FOM enhanced both IL-6 and IL-10 synthesis, CAM enhanced only IL-10 synthesis, but dexamethasone deeply suppressed the synthesis of both cytokines [27].
• Moreover, fosfomycin resistance was imparted to the E. coli strain expressing the chlamydial murA [28].
• Fosfomycin could not suppress the HTLV-I-associated SP, but had the properties to decrease the levels of TGF-beta1 and MIP-1alpha [29].
• Fosfomycin alters lipopolysaccharide-induced inflammatory cytokine production in mice [30].

Analytical, diagnostic and therapeutic context of FOSFOMYCIN

• Fosfomycin kinetics after intravenous and oral administration to human volunteers [31].
• A feasible capillary zone electrophoresis (CZE) method with indirect UV and contactless conductivity detection was developed for the determination of fosfomycin, an antibiotic, in human plasma and microdialysis samples [32].
• With a combination of fosfomycin at three times the MIC and ofloxacin at three times the MIC, complete eradication was confirmed by both ATP assay and scanning electron microscopy [33].
• Titration of MurZ with fosfomycin revealed a stoichiometry of 1 molecule of inhibitor per active site when assessed using either enzyme activity or mass spectrometry as an index of modification [24].
• Capillary electrophoresis analysis of fosfomycin in biological fluids for clinical pharmacokinetic studies [32].

References