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Staphylococcus aureus treated with fosfomycin

ABSTRACT: Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 µg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces “cell wall stimulon” genes and were able to identify genes and pathways specifically modulated by fosfomycin.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE15394 | GEO | 2009/03/26

SECONDARY ACCESSION(S): PRJNA115873

REPOSITORIES: GEO

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Staphylococcus aureus treated with fosfomycin

Project description:Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 Âµg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces âcell wall stimulonâ genes and were able to identify genes and pathways specifically modulated by fosfomycin. Time course, different fosfomycin concentration

2010-05-20 | E-GEOD-15394 | biostudies-arrayexpress

Effects of fosfomycin on biofilm of a clinical Staphylococcus aureus isolated from osteoarticular infection by transcriptomal approach

Project description:The aim of the present study was to investigate the mechanisms by which fosfomycin restrains biofilm formation and affects a 24h-old biofilm of S. aureus. RNA sequencing (RNA-Seq) technology was used to compare the transcriptomes of S. aureus biofilms formed or treated with sublethal concentrations of fosfomycin.

2018-01-31 | GSE83269 | GEO

Fosfomycin uptake in Escherichia coli is mediated by the outer membrane porins OmpF, OmpC and LamB

Project description:The antibiotic fosfomycin is widely recognized for treatment of lower urinary tract infections caused by Escherichia coli and lately gained importance as a therapeutic option to combat multidrug resistant bacteria. Still, resistance to fosfomycin frequently develops through mutations reducing its uptake. Whereas the inner membrane transport of fosfomycin has been extensively studied in E. coli, its outer membrane (OM) transport remains insufficiently understood. While evaluating minimal inhibitory concentrations in OM porin-deficient mutants, we observed that the E. coli ΔompCΔompF strain is five times more resistant to fosfomycin than the wild type and the respective single mutants. Continuous monitoring of cell lysis of porin-deficient strains in response to fosfomycin additionally indicated the relevance of LamB. Furthermore, the physiological relevance of OmpF, OmpC and LamB for fosfomycin uptake was confirmed by electrophysiological and transcriptional analysis. This study expands the knowledge of how fosfomycin crosses the OM of E. coli.

2024-01-24 | GSE236554 | GEO

Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants

Project description:In this work we describe a robust fosfomycin collateral sensitivity phenotype of Pseudomonas aeruginosa resistant mutants selected by antibiotics from different structural families. The underlying mechanism was the reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where the de novo synthesis is blocked, and of fosA, encoding a fosfomycin-inactivating enzyme.

2022-03-02 | GSE153006 | GEO

Fosfomycin and the intermediate metabolites PEP and GA-3P effect on Stenotrophomonas maltophilia transcriptome

Project description:Transcriptomic analysis of S. maltophilia D457 after one-hour induction with the antibiotic fosfomycin, the intermediate metabolites phosphoenolpyruvate or glyceraldehyde-3-phosphate

2022-01-19 | GSE181918 | GEO

Transcriptional response of P. aeruginosa to fosfomycin tobramycin and FT under aerobic and anaerobic conditions

Project description:The experiment aimed to characterise the transcriptional response of a clinical CF P. aeruginosa isolate to sub-inhibitory concentrations of fosfomycin, tobramycin and a novel 4/1 (w/w) combination of the two (FT) under both aerobic and anaerobic conditions

2013-08-28 | E-MEXP-3764 | biostudies-arrayexpress

Agrobacterium tumefaciens Fosfomycin Tn-Seq

Project description:Transposon Sequencing in Agrobacterium tumefaciens treated with Fosfomycin

| PRJEB53499 | ENA

Staphylococcus aureus

Project description:Staphylococcus aureus treated with fosfomycin

| PRJNA115873 | ENA

Transcriptional Profiling of Daptomycin Induced Staphylococcus aureus

Project description:Daptomycin is a lipopeptide antibiotic that has recently been approved for treatment of Gram-positive bacterial infections. The mode of action of daptomycin is not yet entirely clear. To further understand the mechanism transcriptomic analysis of changes in gene expression in daptomycin-treated Staphylococcus aureus was carried out. The expression profile indicated that cell wall stress stimulon member genes (B. J. Wilkinson, A. Muthaiyan, and R. K. Jayaswal. 2005. Curr. Med. Chem. Anti-Infective Agents 4: 259-276) were significantly induced by daptomycin, and by the cell wall-active antibiotics vancomycin and oxacillin. Comparison of the daptomycin response of a two-component cell wall stress stimulon regulator VraSR mutant, S. aureus KVR, to its parent N315 showed diminished expression of the cell wall stress stimulon in the mutant. Daptomycin has been proposed to cause membrane depolarization, and the transcriptional responses to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nisin were determined. Transcriptional profiles of the responses to these antimicrobial agents showed significantly different patterns compared to those of the cell wall-active antibiotics, including little or no induction of the cell wall stress stimulon. However, there were a significant number of genes induced by both CCCP and daptomycin that were not induced by oxacillin or vancomycin, such that the daptomycin transcriptome was probably reflecting a membrane depolarizing activity of this antimicrobial also. The results indicate that inhibition of peptidoglycan biosynthesis, either directly or indirectly, and membrane depolarization are parts of the mode of action of daptomycin. Keywords: mode of action, transcriptional profiling

2007-12-25 | GSE9494 | GEO

Analysis of the sigS regulon

Project description:The sigS gene in S. aureus encodes an ECF sigma factor. ECF sigma factors bind to core-RNA polymerase and redirecting promoter recognition to coordinate gene expression. To determine all of the genes in S. aureus whose expression is SigS dependent we preformed a microarray analysis of a wild type and sigS mutant strain. Genes showing altered expression levels in the sigS mutant versus the wild type were deemed SigS dependent.

2012-02-01 | GSE35336 | GEO

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