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Mechanisms of Resistance

Substrate Spectrum Extension of PenA in Burkholderia thailandensis with a Single Amino Acid Deletion, Glu168del

Hyojeong Yi, Karan Kim, Kwang-Hwi Cho, Oksung Jung, Heenam Stanley Kim
Hyojeong Yi
aDepartment of Medicine, College of Medicine, Korea University, Anam-Dong, Seongbuk-Gu, Seoul, South Korea
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Karan Kim
aDepartment of Medicine, College of Medicine, Korea University, Anam-Dong, Seongbuk-Gu, Seoul, South Korea
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Kwang-Hwi Cho
bSchool of Systems Biomedical Science and Research Center for Integrative Basic Science, Soongsil University, Seoul, South Korea
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Oksung Jung
bSchool of Systems Biomedical Science and Research Center for Integrative Basic Science, Soongsil University, Seoul, South Korea
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Heenam Stanley Kim
aDepartment of Medicine, College of Medicine, Korea University, Anam-Dong, Seongbuk-Gu, Seoul, South Korea
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DOI: 10.1128/AAC.00598-12
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    Fig 1

    A single amino acid deletion mutation in PenA. The PenA protein is represented by an arrow in which four conserved domains of sequences and the omega loop common to class A β-lactamases (11) are indicated. The positions are numbered according to Ambler et al. (1). B. thailandensis strain E264 with the intact penA allele (penA-WT) and others with various penA alleles are listed, and the MICs of ceftazidime (CAZ) are shown in the bar graph. Complemented strains contain the penA alleles, corresponding to the disrupted genes, carried by plasmid pRK415K.

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    Fig 2

    Altered α-helix structure and the internal space in the omega loop of PenA. Glu168del resulted in disruption of the α-helix structure and expansion of the internal space in the omega loop. The measured distances are designated A, B, and C in the simulated three-dimensional omega loop structure. The distance between positions 164 and 179, where the ionic bond is present (at least in the wild type), in PenA-Glu168del is compared to that in the wild type in the bar graph. The distances between positions 164 and 173 and positions 163 and 174 in the omega loop, representing the internal space of the omega loop, are also compared to those in the wild type in the bar graph.

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  • Table 1

    MICs of various β-lactams for B. thailandensis strains

    StrainMIC (μg/ml)a
    AMXAMX-CLACTXMCRXCEFMER
    Wild-type E264 (penA-WT)366616180.75
    Mutant E264 (penA-Glu168del)42.254.52.590.63
    penA-null mutants
        E264 (ΔpenA-WT)41.510.530.75
        E264 (ΔpenA-Glu168del)32.250.750.2230.38
    Complemented penA-null mutantsb
        E264 (ΔpenA-WT, complemented)>25648>32>32640.75
        E264 (ΔpenA-Glu168del, complemented)102.251212481.13
    • ↵a MICs were measured by the Etest. Abbreviations: AMX, amoxicillin; AMX-CLA, amoxicillin-clavulanic acid; CTXM, cefotaxime; CRX, ceftriaxone; CEF, cefepime; MER, meropenem.

    • ↵b Complemented with penA alleles carried by pRK415K.

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Substrate Spectrum Extension of PenA in Burkholderia thailandensis with a Single Amino Acid Deletion, Glu168del
Hyojeong Yi, Karan Kim, Kwang-Hwi Cho, Oksung Jung, Heenam Stanley Kim
Antimicrobial Agents and Chemotherapy Jun 2012, 56 (7) 4005-4008; DOI: 10.1128/AAC.00598-12

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Substrate Spectrum Extension of PenA in Burkholderia thailandensis with a Single Amino Acid Deletion, Glu168del
Hyojeong Yi, Karan Kim, Kwang-Hwi Cho, Oksung Jung, Heenam Stanley Kim
Antimicrobial Agents and Chemotherapy Jun 2012, 56 (7) 4005-4008; DOI: 10.1128/AAC.00598-12
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