1887

Abstract

Borderline oxacillin-resistant (BORSA) exhibit oxacillin MIC values of 1–8 μg ml, but lack , which encodes the low-affinity penicillin-binding protein (PBP)2a. The relationship of the BORSA phenotype with specific genetic backgrounds was assessed, as well as amino acid sequence variation in the normal PBP2. Among 38 BORSA, 26 had a common PFGE profile of genomic DNA, and were multilocus sequence type (ST)25. The other isolates were genetically diverse. Complete sequences were determined for three BORSA, corresponding to ST25, ST1 and ST47, which were selected on the basis of lacking -encoded -lactamase. The essential transpeptidase-domain-encoding segment of was also sequenced from seven additional ST25 isolates. Amino acid substitutions occurred in the transpeptidase domain of all BORSA, irrespective of clonal type. A Gln→Pro substitution was common to all ST25 BORSA, but most could be distinguished from one another by additional unique substitutions in the transpeptidase domain. The ST1 and ST47 isolates also possessed unique substitutions in the transpeptidase domain. Plasmid-mediated expression of from an ST25 or ST1 isolate in RN6390 increased its oxacillin MIC from 0.25 to 4 μg ml, while from a susceptible strain, ATCC 25923, had no effect. Therefore, different amino acid substitutions in PBP2 of diverse BORSA lineages contribute to borderline resistance. The predominant ST25 lineage was not related to any of the five clonal complexes that contain meticillin-resistant (MRSA), suggesting that ST25 cannot readily acquire -mediated resistance.

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2006-12-01
2019-11-20
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