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Mechanisms of Resistance

OXA-28, an Extended-Spectrum Variant of OXA-10 β-Lactamase from Pseudomonas aeruginosa and Its Plasmid- and Integron-Located Gene

Laurent Poirel, Delphine Girlich, Thierry Naas, Patrice Nordmann
Laurent Poirel
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, France
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Delphine Girlich
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, France
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Thierry Naas
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, France
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Patrice Nordmann
Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, France
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DOI: 10.1128/AAC.45.2.447-453.2001
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    Fig. 1.

    Nucleotide sequence of 2,254 bp of recombinant plasmid pDG-1 containing the blaOXA-28 coding region and part of its integron, In57. The deduced amino acid sequence is designated in single-letter code below the nucleotide sequence. The slash indicates the putative clevage site for the leader peptide for the mature OXA-28 β-lactamase. Underlined amino acid sequences are those conserved for the oxacillinase family and are numbered according to DBL numbering (3). The start codons ofintI1, blaOXA-28, andaac(6′)Ib are indicated by horizontal arrows, and their stop codons are indicated by asterisks. The −35 and −10 sequences of the promoters Pc, P2, and Pint are underlined. The conserved core and inverse core sites located at theoxa28 and aac(6′)Ib cassette boundaries are boxed and the composite 59-base elements are italicized. The additional base of the 59-base element of the oxa28 gene cassette as compared to the 59-base element of the oxa19 gene cassette is indicated by a square below the 59-base element of theoxa28 gene cassette. The cassette boundaries are indicated by vertical arrows. The left part of the attI1 site is underlined with a dotted line.

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  • Table 1.

    MICs of β-lactams for the P. aeruginosa ED-1 clinical isolate, its transconjugant P. aeruginosaPU21(pGIR-1), reference strain P. aeruginosa PU21,E. coli DH10B(pDG-1), and reference strain E. coli DH10B

    β-LactamaMIC (μg/ml) for:
    P. aeruginosa ED-1P. aeruginosa PU21 (pGIR-1)bP. aeruginosaPU21E. coli DH10B (pDG-1)bE. coli DH10B
    Amoxicillin>512>51232162
    Ticarcillin6412816322
    Ticarcillin plus CLA6412816321
    Piperacillin8162321
    Piperacillin plus TZB8161161
    Cephalothin>128>128>12884
    Cefsulodin256642322
    Cefuroxime>128>128>12844
    Ceftazidime2565120.251280.06
    Ceftazidime plus CLA128640.25640.06
    Cefotaxime1616240.12
    Cefepime32160.060.5<0.06
    Moxalactam128256810.25
    Aztreonam32320.580.12
    Imipenem20.250.120.060.06
    • ↵a CLA, clavulanic acid at a fixed concentration of 2 μg/ml; TZB, tazobactam at a fixed concentration of 4 μg/ml.

    • ↵b P. aeruginosa PU21 harboring natural plasmid pGIR-1 and E. coli DH10B harboring recombinant plasmid pDG-1 produced the β-lactamase OXA-28.

  • Table 2.

    Amino acid differences among extended-spectrum oxacillinases compared to OXA-10

    OxacillinaseAmino acid(s) at position(s)a:
    1020285870–737692110127144–146164167184208216–218240258272
    OXA-10IGSDS-T-F-KNVTAY-G-NWGYAK-T-GESE
    OXA-M101bL
    OXA-M102bSD
    OXA-M103bK
    OXA-11SD
    OXA-14D
    OXA-16TD
    OXA-17S
    OXA-13TSNSSFGNA
    OXA-13-1bTSNSSDFGNA
    OXA-19TSNSDFGNA
    OXA-28TSNSGFGNA
    • ↵a The standard numbering scheme for class D enzymes (DBL numbering) is used (3). The amino acids in boldface may contribute to the extension of the substrate hydrolysis profile, leading to extended-spectrum derivatives.

    • ↵b In vitro-obtained mutant (9).

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OXA-28, an Extended-Spectrum Variant of OXA-10 β-Lactamase from Pseudomonas aeruginosa and Its Plasmid- and Integron-Located Gene
Laurent Poirel, Delphine Girlich, Thierry Naas, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Feb 2001, 45 (2) 447-453; DOI: 10.1128/AAC.45.2.447-453.2001

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OXA-28, an Extended-Spectrum Variant of OXA-10 β-Lactamase from Pseudomonas aeruginosa and Its Plasmid- and Integron-Located Gene
Laurent Poirel, Delphine Girlich, Thierry Naas, Patrice Nordmann
Antimicrobial Agents and Chemotherapy Feb 2001, 45 (2) 447-453; DOI: 10.1128/AAC.45.2.447-453.2001
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KEYWORDS

Genes, Bacterial
plasmids
Pseudomonas aeruginosa
beta-lactamases

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