Revealing fosfomycin primary effect on Staphylococcus aureus transcriptome: modulation of cell envelope biosynthesis and phosphoenolpyruvate induced starvationReport as inadecuate




Revealing fosfomycin primary effect on Staphylococcus aureus transcriptome: modulation of cell envelope biosynthesis and phosphoenolpyruvate induced starvation - Download this document for free, or read online. Document in PDF available to download.

BMC Microbiology

, 10:159

First Online: 01 June 2010Received: 23 December 2009Accepted: 01 June 2010

Abstract

BackgroundStaphylococcus aureus is a highly adaptable human pathogen and there is a constant search for effective antibiotics. Fosfomycin is a potent irreversible inhibitor of MurA, an enolpyruvyl transferase that uses phosphoenolpyruvate as substrate. The goal of this study was to identify the pathways and processes primarily affected by fosfomycin at the genome-wide transcriptome level to aid development of new drugs.

ResultsS. aureus ATCC 29213 cells were treated with sub-MIC concentrations of fosfomycin and harvested at 10, 20 and 40 minutes after treatment. S. aureus GeneChip statistical data analysis was complemented by gene set enrichment analysis. A visualization tool for mapping gene expression data into biological pathways was developed in order to identify the metabolic processes affected by fosfomycin. We have shown that the number of significantly differentially expressed genes in treated cultures increased with time and with increasing fosfomycin concentration. The target pathway - peptidoglycan biosynthesis - was upregulated following fosfomycin treatment. Modulation of transport processes, cofactor biosynthesis, energy metabolism and nucleic acid biosynthesis was also observed.

ConclusionsSeveral pathways and genes downregulated by fosfomycin have been identified, in contrast to previously described cell wall active antibiotics, and was explained by starvation response induced by phosphoenolpyruvate accumulation. Transcriptomic profiling, in combination with meta-analysis, has been shown to be a valuable tool in determining bacterial response to a specific antibiotic.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2180-10-159 contains supplementary material, which is available to authorized users.

Marko Petek, Špela Baebler contributed equally to this work.

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Author: Marko Petek - Špela Baebler - Drago Kuzman - Ana Rotter - Zdravko Podlesek - Kristina Gruden - Maja Ravnikar - Uroš Urle

Source: https://link.springer.com/article/10.1186/1471-2180-10-159







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