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A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid
Hun-Suk Song1, Tae-Rim Choi1, Yeong-Hoon Han1
1Department of Biological Engineering, College of Engineering, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701, Republic of Korea.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) strains are distinct from general Staphylococcus strains with respect to the composition of the membrane, ability to form a thicker biofilm, and, importantly, ability to modify the target of antibiotics to evade their activity. The agr gene is an accessory global regulator of gram-positive bacteria that governs virulence or resistant mechanisms and therefore an important target for the control of resistant strains. However, the mechanism by which agr impacts resistance to β-lactam antibiotics remains unclear. In the present study, we found the Δagr mutant strain having higher resistance to high concentrations of β-lactam antibiotics such as oxacillin and ampicillin. To determine the influence of variation in the microenvironment of cells between the parental and mutant strains, fatty acid analysis of the supernatant, total lipids, and phospholipid fatty acids were compared. The Δagr mutant strain tended to produce fewer fatty acids and retained lower amounts of C16, C18 fatty acids in the supernatant. Phospholipid analysis showed a dramatic increase in the hydrophobic longer-chain fatty acids in the membrane. To target membrane, we applied several surfactants and found that sorbitan monolaurate (Span20) had a synergistic effect with oxacillin by decreasing biofilm formation and growth. These findings indicate that agr deletion allows for MRSA to resist antibiotics via several changes including constant expression of mecA, fatty acid metabolism, and biofilm thickening.
Insights
The agr gene deletion in Methicillin-resistant Staphylococcus aureus (MRSA) enhances resistance to beta-lactam antibiotics by altering cell membrane fatty acids and increasing biofilm formation. Sorbitan monolaurate (Span20) combined with oxacillin reduces MRSA growth and biofilm.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) exhibits unique membrane composition, biofilm formation, and antibiotic resistance mechanisms.
- The agr gene regulates virulence and resistance in gram-positive bacteria, but its role in beta-lactam antibiotic resistance is not fully understood.
Purpose of the Study:
- To investigate the mechanism by which the agr gene influences MRSA resistance to beta-lactam antibiotics.
- To analyze changes in cell membrane fatty acid composition and biofilm formation in agr-deleted MRSA strains.
Main Methods:
- Comparative analysis of fatty acid composition in the supernatant and lipids of parental and Δagr mutant MRSA strains.
- Investigation of phospholipid fatty acid profiles in the cell membrane.
- Evaluation of the synergistic effect of surfactants, specifically sorbitan monolaurate (Span20), with oxacillin on MRSA growth and biofilm formation.
Main Results:
- The Δagr mutant strain showed increased resistance to high concentrations of oxacillin and ampicillin.
- Δagr mutant strains produced fewer fatty acids in the supernatant, with lower retention of C16 and C18 fatty acids.
- Phospholipid analysis revealed a significant increase in hydrophobic longer-chain fatty acids within the cell membrane of the Δagr mutant.
- Sorbitan monolaurate (Span20) demonstrated a synergistic effect with oxacillin, reducing MRSA biofilm formation and growth.
Conclusions:
- Agr deletion contributes to MRSA antibiotic resistance through mechanisms including constant mecA expression, altered fatty acid metabolism, and enhanced biofilm thickening.
- Targeting the bacterial membrane with agents like sorbitan monolaurate (Span20) can be a viable strategy to overcome MRSA resistance when combined with existing antibiotics.
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