The PBP2a (encoded by mecA gene) in MRSA confers resistance to all β-lactams except newer agents. Which mechanism specifically makes ceftaroline effective against MRSA despite PBP2a?
- A Ceftaroline is a β-lactamase inhibitor that destroys the β-lactamase produced by MRSA
- B Ceftaroline inhibits mecA gene transcription by binding to the promoter region
- C Ceftaroline has an extended side chain that allows it to bind PBP2a with high affinity by inducing an open conformation of its active site ✓
- D Ceftaroline bypasses the cell wall by directly disrupting the cytoplasmic membrane like daptomycin
Correct answer: C. Ceftaroline has an extended side chain that allows it to bind PBP2a with high affinity by inducing an open conformation of its active site
Explanation
PBP2a has an allosteric site distinct from its active site. Ceftaroline (a 5th-generation cephalosporin) first binds to this allosteric site, triggering a conformational change that opens the active site, after which the drug also binds the active site, irreversibly acylating it. This 'two-site' mechanism overcomes the low-affinity problem that makes standard β-lactams ineffective against MRSA. Ceftaroline is the only β-lactam currently approved for MRSA skin and soft tissue infections and pneumonia.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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