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Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant
F Najioullah1, G Pellon, J Freney
1Laboratoire Central de Microbiologie, Hôpital Edouard Herriot, Lyon, France.
Abstract:
The effects of fosfomycin on penicillin-binding proteins (PBPs) were studied on the methicillin-resistant Staphylococcus aureus strain CIP (Collection de l'Institut Pasteur, Paris, France) 65-25 and on a methicillin-susceptible S. aureus strain CIP 65-6. The combinations of fosfomycin and oxacillin were synergistic, additive or antagonistic, depending on antibiotic concentrations. Fosfomycin induced modifications of the PBP profile of the two strains studied. In particular, it increased the expression of PBP2. This suggested that this protein is inducible; the only PBP not affected by fosfomycin was PBP3.
Insights
Fosfomycin alters penicillin-binding proteins (PBPs) in Staphylococcus aureus, notably increasing PBP2 expression. This impacts antibiotic combinations, suggesting PBP2 is inducible and PBP3 is unaffected by fosfomycin.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Penicillin-binding proteins (PBPs) are crucial targets for beta-lactam antibiotics.
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat.
- Understanding antibiotic-PBP interactions is key to developing new treatment strategies.
Purpose of the Study:
- To investigate the effects of fosfomycin on penicillin-binding proteins (PBPs) in both methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains.
- To evaluate the synergistic, additive, or antagonistic interactions between fosfomycin and oxacillin.
Main Methods:
- Studied methicillin-resistant Staphylococcus aureus (MRSA) strain CIP 65-25 and methicillin-susceptible S. aureus strain CIP 65-6.
- Analyzed the impact of fosfomycin on PBP profiles.
- Examined combinations of fosfomycin and oxacillin at varying concentrations.
Main Results:
- Fosfomycin induced modifications in the PBP profiles of both S. aureus strains.
- Fosfomycin significantly increased the expression of PBP2.
- The interaction between fosfomycin and oxacillin varied (synergistic, additive, or antagonistic) based on antibiotic concentrations.
Conclusions:
- Fosfomycin influences PBP expression in Staphylococcus aureus, particularly inducing PBP2.
- PBP2 appears to be an inducible protein in response to fosfomycin.
- PBP3 was the only PBP not affected by fosfomycin treatment.