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Staphylococcus pseudintermedius's PBP4 Is Directly Associated with the Dissociated Oxacillin and Cefoxitin Phenotype
Paula Gagetti1, Roberto R Rosato2, Adriana E Rosato3,4
1Servicio Antimicrobianos, INEI-ANLIS, Buenos Aires 1281, Argentina.
Abstract:
Staphylococcus pseudintermedius is an important pathogen responsible for infections in dogs and in humans. The emergence and dissemination of methicillin-resistant S. pseudintermedius (MRSP) and the multidrug resistance frequently seen in this species make difficult the treatment of these pathogens. The cefoxitin disk is widely used as a marker of methicillin resistance mediated by the mecA gene in Staphylococcus aureus and other staphylococcal species; however, it is not useful to detect β-lactam resistance of MRSP in clinical microbiology laboratories. The purpose of this study was to elucidate the molecular bases of the dissociated phenotype between oxacillin and cefoxitin antibiotics. By using a combinatorial approach that included the Penicillin-Binding Proteins' (PBP) profile, their affinity for different β-lactam antibiotics and the analyses of PBPs' sequence, we provide evidence that PBP4 showed still affinity for its target cefoxitin, impairing its phenotypic resistant detection in MRSP. Together, these findings provide evidence that S. pseudintermedius PBP4 is directly associated with the dissociated oxacillin and cefoxitin phenotype.
Insights
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) poses treatment challenges. This study reveals that PBP4
Area of Science:
- Veterinary Microbiology
- Antimicrobial Resistance
- Molecular Biology
Background:
- Staphylococcus pseudintermedius is a significant pathogen in veterinary and human medicine.
- The rise of multidrug-resistant strains, including methicillin-resistant S. pseudintermedius (MRSP), complicates treatment.
- Current laboratory methods using cefoxitin disks are insufficient for detecting MRSP's beta-lactam resistance.
Purpose of the Study:
- To investigate the molecular mechanisms behind the differing resistance patterns to oxacillin and cefoxitin in MRSP.
- To understand why cefoxitin disk tests fail to accurately detect methicillin resistance in S. pseudintermedius.
Main Methods:
- Analysis of Penicillin-Binding Proteins (PBP) profiles in MRSP.
- Assessment of PBP affinity for various beta-lactam antibiotics.
- Sequencing of PBP genes to identify resistance-associated mutations.
Main Results:
- Penicillin-Binding Protein 4 (PBP4) retains affinity for cefoxitin in MRSP.
- This retained affinity of PBP4 for cefoxitin interferes with the accurate phenotypic detection of resistance.
- The study identified PBP4 as the key factor in the dissociated oxacillin and cefoxitin resistance phenotype.
Conclusions:
- Staphylococcus pseudintermedius PBP4 is directly implicated in the discordant oxacillin and cefoxitin resistance.
- Understanding this mechanism is crucial for accurate diagnosis and effective treatment of MRSP infections.
- This finding highlights the need for revised diagnostic strategies for MRSP in clinical microbiology.
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