Characterization of the
 fomA
 and
 fomB
 Gene Products from
 Streptomyces wedmorensis
 , Which Confer Fosfomycin Resistance on
 Escherichia coli

Kobayashi, Seiji; Kuzuyama, Tomohisa; Seto, Haruo

doi:10.1128/aac.44.3.647-650.2000

Cited by 59 publications

(51 citation statements)

References 15 publications

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“…It has been described in P. syringae, a species that naturally produces fosfomycin. 29 A similar mechanism has been described with fomA and fomB in Streptomyces wedmorensis, 108 and with rare strains of P. aeruginosa. 109 • FosX leads to a water adduct.…”

Section: Mechanisms Of Resistancesupporting

confidence: 53%

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

2011

Clinical Medicine Reviews in Therapeutics

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Abstract:The use of fosfomycin has been limited in therapeutics in recent years. Because it has shown good antibacterial activity in vitro and clinical efficacy in some domains, it has been proposed as an alternative to current antimicrobial agents, which are subject to increasing resistance. This paper reviews the main properties of fosfomycin and the latest publications concerning multidrugresistant Enterobacteriaceae infections. In uncomplicated urinary tract infections, a single oral dose was found to be safe and effective. In complicated urinary tract infections, the same results were observed with several doses. In both cases, by using fosfomycin to treat infections, the use of carbapenems could be reduced, leading to lower costs and better microbial ecology. In severe infections, combinations with intravenous fosfomycin need to be explored further because its future activity may depend on choosing a good partner drug. Because of the fast evolution of microbial resistance, more studies are urgently needed.

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Section: Mechanisms Of Resistancesupporting

confidence: 53%

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

2011

Clinical Medicine Reviews in Therapeutics

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“…1), a gene encoding the epoxidase was present (here designated psf4). An ortholog of the fomA gene (psf7), which has previously been shown to encode a protein that confers self-resistance by phosphorylating fosfomycin (16,31,35,42), was also present. However, a gene encoding a FomB ortholog, another protein involved in self-resistance in fosfomycin-producing streptomycetes by converting the compound to its bisphosphorylated analog (31, 35), was not found in the PB-5123 genome.…”

Section: Resultsmentioning

confidence: 99%

“…The phosphonomethylmalate synthase activity of the His 6 -tagged Psf2 was assayed by 31 P NMR spectroscopy and Fourier transform mass spectrometry (FTMS). The assay mixture (1 ml) contained 50 mM HEPES-K ϩ (pH 7.2), 5 mM MgCl 2 , 0.3 mM acetyl coenzyme A (Ac-CoA), 5 mM PEP, 10 M Psf1, and 50 M Psf2.…”

Section: Methodsmentioning

confidence: 99%

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Different Biosynthetic Pathways to Fosfomycin in Pseudomonas syringae and Streptomyces Species

Kim

Metcalf

et al. 2012

Antimicrob Agents Chemother

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cFosfomycin is a wide-spectrum antibiotic that is used clinically to treat acute cystitis in the United States. The compound is produced by several strains of streptomycetes and pseudomonads. We sequenced the biosynthetic gene cluster responsible for fosfomycin production in Pseudomonas syringae PB-5123. Surprisingly, the biosynthetic pathway in this organism is very different from that in Streptomyces fradiae and Streptomyces wedmorensis. The pathways share the first and last steps, involving conversion of phosphoenolpyruvate to phosphonopyruvate (PnPy) and 2-hydroxypropylphosphonate (2-HPP) to fosfomycin, respectively, but the enzymes converting PnPy to 2-HPP are different. The genome of P. syringae PB-5123 lacks a gene encoding the PnPy decarboxylase found in the Streptomyces strains. Instead, it contains a gene coding for a citrate synthase-like enzyme, Psf2, homologous to the proteins that add an acetyl group to PnPy in the biosynthesis of FR-900098 and phosphinothricin. Heterologous expression and purification of Psf2 followed by activity assays confirmed the proposed activity of Psf2. Furthermore, heterologous production of fosfomycin in Pseudomonas aeruginosa from a fosmid encoding the fosfomycin biosynthetic cluster from P. syringae PB-5123 confirmed that the gene cluster is functional. Therefore, two different pathways have evolved to produce this highly potent antimicrobial agent.

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“…Fosfomycin has a low molecular weight with a relatively long half-life post intake (mean half life-SD, 5.7-2.8 h) and therefore, penetrates various tissues with ease, achieving the minimum inhibitory concentrations needed to inhibit the growth of most of the pathogens (16). Resistance emergence rate is low and most frequently acquired by chromosomal mutations that do not spread easily (17). In previous studies, around 10% of strains of Ps.…”

Section: Key: (S)= Sensitive (R)= Resistantmentioning

confidence: 99%

In vitro activity of fosfomycin against uropathogen multi-drug resistant (MDR) Pseudomonas aeruginosa and Acinetobacter baumannii

Rasool¹,

Ajaz²,

Siddiqui³

et al. 2015

Af J Clin Exp Micro

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Urinary tract infections caused by multidrug resistant Gram negative bacilli constitute a major global healthcare problem. Fosfomycin is considered the best treatment option for such infections. Urine samples were collected and cultured in a tertiary care hospital (Urology). Identification of these uropathogens and their antibiotic sensitivity screening were performed according to CLSI guidelines. Urine samples (n=436) were selected in which Ps. aeruginosa and Acinetobacter baumannii were found to be the significant pathogens and treated-exposed to fosfomycin. Sixty six (15%) were identified as Acinetobacter baumannii, Ps. aeruginosa n=370(85%). Forty four percent of all Ps. aeruginosa were found to be multidrug resistant while 48.5% of the Acinetobacter baumannii strains were found multidrug resistant. Polymyxin B was found to be the most effective drug (100%) against all uropathogens and fosfomycin was found effective against 73% of the multidrug resistant Acinetobacter baumannii isolates and 70% of the multidrug resistant Pseudomonas aeruginosa strains. It may be concluded that antimicrobial activity (in vitro) of fosfomycin, especially against MDR uropathogens, is very effective.

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Characterization of the fomA and fomB Gene Products from Streptomyces wedmorensis , Which Confer Fosfomycin Resistance on Escherichia coli

Cited by 59 publications

References 15 publications

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

Different Biosynthetic Pathways to Fosfomycin in Pseudomonas syringae and Streptomyces Species

<i>In vitro</i> activity of fosfomycin against uropathogen multi-drug resistant (MDR)<i> Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>

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