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A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
The mevalonate pathway of Staphylococcus aureus
Carl J Balibar1, Xiaoyu Shen, Jianshi Tao
1Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, MA 02139, USA.
Journal of Bacteriology
|November 26, 2008
Summary
Downregulating the mevalonate pathway in Staphylococcus aureus significantly alters gene expression, decreasing primary metabolism while increasing virulence factors and cell wall components. Compensatory isoprenoid gene expression was minimal.
Area of Science:
- Microbiology
- Metabolic Engineering
- Systems Biology
Background:
- Isoprenoids are vital organic molecules synthesized from isopentenyl pyrophosphate (IPP).
- Bacterial isoprenoid pathways are crucial for cell wall formation and energy generation but remain poorly understood.
- The mevalonate pathway produces IPP in many bacteria and eukaryotes.
Purpose of the Study:
- To investigate cellular responses to mevalonate pathway perturbations in Staphylococcus aureus.
- To profile transcriptional changes upon downregulation of mevalonate pathway genes.
Main Methods:
- Constructed three IPTG-inducible promoter strains of Staphylococcus aureus.
- Utilized DNA microarrays for transcriptional profiling.
- Correlated transcriptional changes with metabolic consequences.
Main Results:
- Decreased mevalonate pathway expression led to widespread downregulation of primary metabolism genes.
- Observed upregulation of virulence factors and cell wall biosynthetic determinants.
- Found minimal compensatory expression in other isoprenoid biosynthetic genes.
Conclusions:
- Mevalonate pathway regulation significantly impacts Staphylococcus aureus primary metabolism and virulence.
- Targeting the mevalonate pathway offers potential strategies for controlling bacterial growth and pathogenesis.
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