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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
Published on: May 8, 2013
Factors influencing methicillin resistance in staphylococci
Brigitte Berger-Bächi1, Susanne Rohrer
1Institute of Medical Microbiology, University of Zürich, Gloriastrasse 32, PO Box, 8028 Zürich, Switzerland. bberger@immv.unizh.ch
Abstract:
Methicillin resistance in staphylococci is due to an acquired penicillin-binding protein, PBP2' (PBP2a). This additional PBP, encoded by mecA, confers an intrinsic resistance to all beta-lactams and their derivatives. Resistance levels in methicillin-resistant Staphylococcus aureus (MRSA) depend on efficient PBP2' production and are modulated by chromosomal factors. Depending on the genetic background of the strain that acquired mecA, resistance levels range from phenotypically susceptible to highly resistant. Characteristic for most MRSA is the heterogeneous expression of resistance, which is due to the segregation of a more highly resistant subpopulation upon challenge with methicillin. Maximal expression of resistance by PBP2' requires the efficient and correct synthesis of the peptidoglycan precursor. Genes involved in cell-wall precursor formation and turnover, regulation, transport, and signal transduction may determine the level of resistance that is expressed. At this stage, however, there is no information available on the functionality or efficacy of such factors in clinical isolates in relation to methicillin resistance levels.
Insights
Methicillin resistance in staphylococci stems from acquired penicillin-binding protein PBP2a, encoded by mecA. Resistance levels in MRSA are influenced by PBP2a production and chromosomal factors, varying widely among strains.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Methicillin resistance in staphylococci is a significant clinical concern.
- The mecA gene encodes an altered penicillin-binding protein, PBP2a, responsible for intrinsic resistance to beta-lactam antibiotics.
- Resistance levels in MRSA are variable and influenced by multiple factors.
Purpose of the Study:
- To investigate the mechanisms underlying varying levels of methicillin resistance in Staphylococcus aureus (MRSA).
- To explore the role of chromosomal factors in modulating PBP2a production and resistance expression.
- To understand the heterogeneous expression of resistance in MRSA populations.
Main Methods:
- Analysis of mecA gene presence and PBP2a expression in clinical MRSA isolates.
- Investigation of genetic backgrounds and chromosomal factors associated with different resistance phenotypes.
- Assessment of cell-wall precursor synthesis and related gene functions in relation to resistance levels.
Main Results:
- MRSA resistance levels are determined by PBP2a production efficiency, modulated by chromosomal elements.
- Genetic background significantly impacts the range of resistance, from susceptible to highly resistant phenotypes.
- Heterogeneous resistance expression in MRSA is linked to subpopulations exhibiting higher resistance upon methicillin challenge.
Conclusions:
- PBP2a production and chromosomal factors are key determinants of MRSA resistance levels.
- Understanding the interplay between mecA and host genetics is crucial for predicting and managing MRSA infections.
- Further research is needed to elucidate the specific roles of cell-wall synthesis and regulatory genes in clinical MRSA isolates.
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