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Updated: Sep 30, 2025

A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
Untargeted lipidomic differences between clinical strains of methicillin-sensitive and methicillin-resistant
Philip Nikolic1, Poonam Mudgil1, David G Harman1
1School of Medicine, Western Sydney University, Penrith, Australia.
Background:
Staphylococcus aureus is a common cause of infectious diseases in humans. It has become resistant to many antibacterial agents making management of infections difficult. A better understanding of differences among S. aureus strains that are sensitive and resistant to antibiotics may offer insights into the resistant phenotype and identify new antimicrobial targets. This study aimed at comparing general differences in lipid profiles among clinical strains of S. aureus sensitive and resistant to antibiotics. The cell wall thickness and cell surface charge were also compared.
Methods:
Five methicillin sensitive (MSSA) and five methicillin resistant (MRSA) S. aureus strains were compared both individually and as MSSA and MRSA groups in the absence of antibiotics. Lipids were compared by ultra-performance liquid chromatography-mass spectrometry, cell wall thickness was compared by scanning transmission electron microscopy and whole-cell surface charge was compared using a cytochrome c binding assay.
Results:
Twenty-two lipid species were identified in all ten strains of S. aureus. The abundance of three lipid species (two lysyl-phosphatidylglycerol and one diglycosyldiacylglycerol) were found to be different between MSSA and MRSA. Differences in cell wall thickness were identified between strains but not between MSSA and MRSA. No difference in whole-cell surface charge was observed between MSSA and MRSA.
Conclusion:
This study shows differences in membrane lipids between antibiotic sensitive and antibiotic resistant clinical strains of S aureus that may affect resistance mechanisms related to cell membrane structure and fluidity. Further research on these differences may identify new drug targets against resistant strains.
Insights
Differences in membrane lipids were observed between antibiotic-sensitive and antibiotic-resistant Staphylococcus aureus strains. These findings may reveal new drug targets for combating resistant bacterial infections.
Area of Science:
- Microbiology
- Biochemistry
- Drug Discovery
Background:
- Staphylococcus aureus is a frequent cause of human infections.
- Antibiotic resistance in S. aureus complicates infection management.
- Understanding strain differences can identify new antimicrobial targets.
Purpose of the Study:
- Compare lipid profiles between antibiotic-sensitive and resistant S. aureus strains.
- Investigate differences in cell wall thickness and surface charge.
Main Methods:
- Compared five methicillin-sensitive (MSSA) and five methicillin-resistant (MRSA) S. aureus strains.
- Utilized ultra-performance liquid chromatography-mass spectrometry for lipid analysis.
- Employed scanning transmission electron microscopy and cytochrome c binding assay for cell wall and surface charge analysis.
Main Results:
- Identified 22 lipid species across all strains.
- Found significant differences in three lipid species (lysyl-phosphatidylglycerol and diglycosyldiacylglycerol) between MSSA and MRSA.
- Observed strain-specific differences in cell wall thickness but not between MSSA and MRSA groups.
- No difference in whole-cell surface charge was detected between MSSA and MRSA.
Conclusions:
- S. aureus strains exhibit distinct membrane lipid profiles correlating with antibiotic sensitivity.
- These lipid differences may influence antibiotic resistance mechanisms.
- Further research into these membrane lipid variations could identify novel therapeutic targets against resistant S. aureus.

