Microbiology · Antimicrobial Resistance Mechanisms and Susceptibility Testing (ESBL, MRSA, VRE, CRE, MIC/MBC, E-test)

A 60-year-old patient with a hip prosthesis develops a peri-prosthetic joint infection (PJI). Cultures from intraoperative tissue samples grow coagulase-negative Staphylococcus (CoNS) resistant to oxacillin (MIC >4 μg/mL). The molecular basis of oxacillin resistance in CoNS is:

  • A mecA gene encoding PBP2a — a modified penicillin-binding protein with low affinity for all beta-lactams
  • B blaZ gene encoding staphylococcal penicillinase that hydrolyzes oxacillin's beta-lactam ring
  • C vanA gene cluster encoding D-Ala-D-Lac ligase altering the peptidoglycan precursor
  • D cfr gene encoding 23S rRNA methylase conferring cross-resistance to beta-lactams
Correct answer: A. mecA gene encoding PBP2a — a modified penicillin-binding protein with low affinity for all beta-lactams

Explanation

Oxacillin/methicillin resistance in staphylococci (both S. aureus/MRSA and coagulase-negative staphylococci) is mediated by the mecA gene (carried on a mobile element called SCCmec). mecA encodes PBP2a (also called PBP2'), an alternative penicillin-binding protein with very low affinity for all beta-lactam antibiotics, rendering them unable to inhibit peptidoglycan synthesis. The mecA gene is detected by PCR-based assays in diagnostic labs. blaZ encodes a beta-lactamase that hydrolyzes penicillin but not oxacillin (isoxazolyl penicillins are beta-lactamase stable). vanA confers glycopeptide resistance. cfr confers phenicol/oxazolidinone/pleuromutilin resistance.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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