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Structural changes induced by mupirocin in Staphylococcus aureus cells
D G Thomas1, A C Hann, M J Day
1Welsh School of Pharmacy, Cardiff University, UK.
Abstract:
Cells of mupirocin-sensitive, moderately-resistant and highly-resistant cultures of Staphylococcus aureus (mupirocin MICs 0.13, 16 and > 512 mg/l, respectively) were exposed to various concentrations of the antibiotic and examined by transmission electron microscopy. The most severe damage occurred in mupirocin-sensitive cells. Cells from moderately-resistant cultures trained in vitro to high-level mupirocin resistance were more hydrophobic than the parent cells. The antibiotic was slowly lethal to the mupirocin-sensitive strain and sub-inhibitory concentrations prevented or reduced growth of the other strains over a 6 h incubation period, irrespective of whether the drug was added at zero time or in the exponential growth phase.
Insights
Mupirocin antibiotic causes severe damage to sensitive Staphylococcus aureus cells. Resistant strains show reduced growth with sub-inhibitory concentrations, indicating potential for new treatment strategies.
Area of Science:
- Microbiology
- Bacterial Resistance
- Electron Microscopy
Background:
- Mupirocin is a key antibiotic for treating Staphylococcus aureus infections.
- Understanding the cellular effects of mupirocin is crucial for combating antibiotic resistance.
- Staphylococcus aureus exhibits varying degrees of mupirocin resistance.
Purpose of the Study:
- To investigate the ultrastructural changes in Staphylococcus aureus cells with different mupirocin resistance levels.
- To compare the impact of mupirocin on sensitive versus resistant strains of Staphylococcus aureus.
- To analyze the effect of sub-inhibitory mupirocin concentrations on bacterial growth.
Main Methods:
- Exposure of mupirocin-sensitive, moderately-resistant, and highly-resistant Staphylococcus aureus cultures to mupirocin.
- Examination of cellular damage using transmission electron microscopy.
- Growth curve analysis under various mupirocin concentrations and incubation times.
Main Results:
- Mupirocin caused the most significant cellular damage in sensitive Staphylococcus aureus strains.
- Moderately-resistant strains, when trained in vitro, exhibited increased cell surface hydrophobicity.
- Sub-inhibitory mupirocin concentrations inhibited or reduced the growth of resistant strains over 6 hours.
Conclusions:
- Mupirocin's lethal effects are most pronounced in sensitive Staphylococcus aureus.
- Cellular adaptations, like increased hydrophobicity, may contribute to mupirocin resistance.
- Sub-inhibitory concentrations of mupirocin can impact the growth of resistant strains, suggesting complex resistance mechanisms.