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A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
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Revealing fosfomycin primary effect on Staphylococcus aureus transcriptome: modulation of cell envelope biosynthesis

Marko Petek1, Spela Baebler, Drago Kuzman

  • 1Department of Biotechnology and Systems Biology, National Institute of Biology, Vecna pot 111, Ljubljana, SI-1000, Slovenia. marko.petek@nib.si

BMC Microbiology
|June 3, 2010
PubMed
Abstract

Insights

Fosfomycin disrupts Staphylococcus aureus by affecting multiple cellular processes, including peptidoglycan biosynthesis. This study reveals novel bacterial responses to fosfomycin, aiding new antibiotic development.

Area of Science:

  • Microbiology and Molecular Biology
  • Bacterial Pathogenesis
  • Antimicrobial Drug Discovery

Background:

  • Staphylococcus aureus is a significant human pathogen requiring new antibiotic treatments.
  • Fosfomycin inhibits MurA, a key enzyme in bacterial cell wall synthesis.
  • Understanding fosfomycin's genome-wide effects is crucial for developing novel therapeutics.

Purpose of the Study:

  • To identify cellular pathways and processes impacted by fosfomycin at the transcriptome level.
  • To analyze the genome-wide gene expression changes in Staphylococcus aureus treated with fosfomycin.
  • To inform the development of new antimicrobial drugs targeting bacterial pathways.

Main Methods:

  • Treatment of Staphylococcus aureus ATCC 29213 with sub-inhibitory concentrations of fosfomycin.
  • Gene expression analysis using GeneChip and gene set enrichment analysis at 10, 20, and 40 minutes.
  • Development of a visualization tool to map gene expression data onto biological pathways.

Main Results:

  • The number of differentially expressed genes increased with time and fosfomycin concentration.
  • Peptidoglycan biosynthesis pathway was upregulated post-fosfomycin treatment.
  • Modulation observed in transport, cofactor biosynthesis, energy metabolism, and nucleic acid biosynthesis pathways.

Conclusions:

  • Fosfomycin downregulates several pathways, distinct from other cell wall antibiotics, due to phosphoenolpyruvate accumulation.
  • A starvation response is induced by fosfomycin, contributing to its antimicrobial effect.
  • Transcriptomic profiling combined with meta-analysis is effective for studying bacterial antibiotic responses.

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