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Updated: May 5, 2026
A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
Identifying potential therapeutic targets of methicillin-resistant Staphylococcus aureus through in vivo proteomic
Binh An Diep1, Qui Phung, Shailesh Date
1Department of Medicine, University of California, San Francisco.
Background:
Detailed knowledge on protein repertoire of a pathogen during host infection is needed for both developing a better understanding of the pathogenesis and defining potential therapeutic targets. Such data, however, have been missing for Staphylococcus aureus, a major human pathogen.
Methods:
We determined the surface proteome of methicillin-resistant S. aureus (MRSA) clone usa300 derived directly from murine systemic infectiON.
Results:
The majority of the in vivo-expressed surface-associated proteins were lipoproteins involved in nutrient acquisition, especially uptake of metal ions. Enzyme-linked immunosorbent assay (ELISA) of convalescent human serum samples revealed that proteins that were highly produced during murine experimental infection were also produced during natural human infection. We found that among the 7 highly abundant lipoproteins only MntC, which is the manganese-binding protein of the MntABC system, was essential for MRSA virulence during murine systemic infection. Moreover, we show that MntA and MntB are equally important for MRSA virulence.
Conclusions:
Besides providing experimental evidence that MntABC might be a potential therapeutic target for the development of antibiotics, our in vivo proteomics data will serve as a valuable basis for defining potential antigen combinations for multicomponent vaccines.
Insights
Staphylococcus aureus surface proteins, particularly those involved in metal ion uptake like MntC, are crucial for virulence. Targeting the MntABC system could lead to new antibiotics and vaccines against this pathogen.
Area of Science:
- Microbiology
- Proteomics
- Infectious Diseases
Background:
- Understanding pathogen protein expression during infection is key for developing therapeutics.
- Detailed proteomic data for Staphylococcus aureus during host infection was previously lacking.
Purpose of the Study:
- To determine the surface proteome of methicillin-resistant Staphylococcus aureus (MRSA) during systemic infection.
- To identify potential therapeutic targets and vaccine antigens.
Main Methods:
- Analysis of the surface proteome of MRSA clone usa300 directly from infected murine models.
- Enzyme-linked immunosorbent assay (ELISA) using convalescent human serum samples.
Main Results:
- The majority of in vivo-expressed surface proteins were lipoproteins involved in nutrient acquisition, especially metal ion uptake.
- Proteins highly produced during murine infection were also found in human infections.
- The MntABC system, particularly MntC, MntA, and MntB, was essential for MRSA virulence.
Conclusions:
- The MntABC system represents a potential therapeutic target for novel antibiotic development.
- In vivo proteomics data provides a basis for designing multicomponent vaccines against Staphylococcus aureus.
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