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New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity

Tomasz, A, Drugeon, H B, de Lencastre, H M, Jabes, D, McDougall, L, Bille, J·1989·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.33.11.1869
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Abstract

Seventeen clinical isolates of Staphylococcus aureus (from the United States and Europe) selected for low (borderline)-level methicillin resistance (MIC of methicillin, 2 to 4 micrograms/ml; MIC of oxacillin, 0.5 to 8 micrograms/ml) were examined for their mechanisms of resistance. Five strains were typical of heterogeneous S. aureus: they gave positive reactions with a DNA probe specific for mec and contained a small fraction (10(-6] of highly resistant cells (MIC, greater than 100 micrograms/ml). The rest of the 12 strains were homogeneous with respect to their methicillin resistance: the MIC of methicillin for all cells was 2 to 4 micrograms/ml, and no cells for which MICs were 50 micrograms/ml or higher were detectable (less than 10(-9]. None of these strains reacted with the mec-specific DNA probe. One representative strain of each group was characterized in more detail. Strain CDC-1, prototype of heterogeneous methicillin-resistant S. aureus, contained penicillin-binding protein (PBP) 2a; its DNA could transform a methicillin-susceptible and novobiocin-resistant recipient to methicillin resistance with ca. 35% linkage to Novr. Introduction of the "factor X" determinant (K. Murakami and A. Tomasz, J. Bacteriol. 171:874-879, 1989) converted strain CDC-1 to high, homogeneous resistance. Strain CDC-6, prototype of the second group of isolates, showed completely homogeneous MICs of methicillin, oxacillin, and cefotaxime. The strain contained modified "normal" PBPs: PBPs 1 and 2 showed low drug reactivity (and/or cellular amounts), and PBP 4 was present in elevated amounts. No PBP 2a could be detected. DNA isolated from strain CDC-6 could transform the methicillin-susceptible and novobiocin-resistant strain to methicillin resistance in a multistep fashion, but this resistance showed no genetic linkage to the Nov marker. We suggest that staphylococci with borderline resistance may contain at least three different classes of mechanism: heterogeneous, methicillin-resistant S. aureus, PBPs of modified drug reactivities, and the previously reported hyperproduction of beta-lactamase (L.K. McDougal and C. Thornsberry, J. Clin Microbiol. 23:832-839, 1986).

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Metadata

Authors
Tomasz, A., Drugeon, H. B., de Lencastre, H. M., Jabes, D., McDougall, L., & Bille, J.
Affiliations
Rockefeller University, New York, New York 10021.
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
1989-11
Volume
33
Issue
11
Pages
1869-1874
ISSN
  • 0066-4804
  • 1098-6596
DOI
10.1128/aac.33.11.1869
Cited by
223
References
0
Language
en
Licence
journals.asm.org/non-commercial-tdm-license (tdm)

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CoChat. (2026). Citation check: New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. https://app.cochat.ai/papers/10.1128/aac.33.11.1869
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Tomasz, A., Drugeon, H. B., de Lencastre, H. M., Jabes, D., McDougall, L., & Bille, J. (1989). New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.33.11.1869

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