Polymorphisms in the type A blaZ gene as determinants of the cefazolin inoculum effect in Staphylococcus aureus

Antimicrob Agents Chemother. 2024 Dec 10:e0110624. doi: 10.1128/aac.01106-24. Online ahead of print.

Abstract

Plasmids containing the wild-type (WT) or mutant type A blaZ (blaZA) gene (mutations at codons 226, 229, or both 226 and 229) were constructed and transformed into Staphylococcus aureus RN4220, yielding the strains WT-blaZ, M226-blaZ, M229-blaZ, and MB-blaZ. The high-inoculum cefazolin MIC was significantly lower in MB-blaZ and M226-blaZ than in WT-blaZ but not in M229-blaZ, suggesting that the single nucleotide polymorphism at codon 226 in blaZA contributes to the cefazolin inoculum effect.

Keywords: Staphylococcus aureus; beta-lactamase; cefazolin; inoculum effect; polymorphism.