Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification

Sunisa Chirakul; Nawarat Somprasong; Michael H. Norris; Vanaporn Wuthiekanun; Narisara Chantratita; Apichai Tuanyok; Herbert P. Schweizer

doi:10.1016/j.ijantimicag.2019.01.003

Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification

Sunisa Chirakul, Nawarat Somprasong, Michael H. Norris, Vanaporn Wuthiekanun, Narisara Chantratita, Apichai Tuanyok, Herbert P. Schweizer

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant CAZ resistance only when overexpressed due to a promoter mutation, transcriptional antitermination or by gene duplication and amplification (GDA). Here we characterise a reversible 33-kb GDA event involving wild-type penA in a CAZ-resistant B. pseudomallei clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 bp) chromosomal sequences, which in this example consist of 4-bp repeats flanked by 3-bp inverted repeats. GDA involving β-lactamases may be a common CAZ resistance mechanism in B. pseudomallei.

Original language	English (US)
Pages (from-to)	582-588
Number of pages	7
Journal	International Journal of Antimicrobial Agents
Volume	53
Issue number	5
DOIs	https://doi.org/10.1016/j.ijantimicag.2019.01.003
State	Published - May 2019
Externally published	Yes

Keywords

Amplification
Burkholderia pseudomallei
Ceftazidime
Gene duplication
Resistance
β-Lactamase

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases
Pharmacology (medical)

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10.1016/j.ijantimicag.2019.01.003

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title = "Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification",

abstract = "Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant CAZ resistance only when overexpressed due to a promoter mutation, transcriptional antitermination or by gene duplication and amplification (GDA). Here we characterise a reversible 33-kb GDA event involving wild-type penA in a CAZ-resistant B. pseudomallei clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 bp) chromosomal sequences, which in this example consist of 4-bp repeats flanked by 3-bp inverted repeats. GDA involving β-lactamases may be a common CAZ resistance mechanism in B. pseudomallei.",

keywords = "Amplification, Burkholderia pseudomallei, Ceftazidime, Gene duplication, Resistance, β-Lactamase",

author = "Sunisa Chirakul and Nawarat Somprasong and Norris, {Michael H.} and Vanaporn Wuthiekanun and Narisara Chantratita and Apichai Tuanyok and Schweizer, {Herbert P.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

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doi = "10.1016/j.ijantimicag.2019.01.003",

language = "English (US)",

volume = "53",

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T1 - Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification

AU - Chirakul, Sunisa

AU - Somprasong, Nawarat

AU - Norris, Michael H.

AU - Wuthiekanun, Vanaporn

AU - Chantratita, Narisara

AU - Tuanyok, Apichai

AU - Schweizer, Herbert P.

PY - 2019/5

Y1 - 2019/5

N2 - Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant CAZ resistance only when overexpressed due to a promoter mutation, transcriptional antitermination or by gene duplication and amplification (GDA). Here we characterise a reversible 33-kb GDA event involving wild-type penA in a CAZ-resistant B. pseudomallei clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 bp) chromosomal sequences, which in this example consist of 4-bp repeats flanked by 3-bp inverted repeats. GDA involving β-lactamases may be a common CAZ resistance mechanism in B. pseudomallei.

AB - Ceftazidime (CAZ) is the antibiotic of choice for the treatment of Burkholderia pseudomallei infection (melioidosis). The chromosomally-encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant CAZ resistance only when overexpressed due to a promoter mutation, transcriptional antitermination or by gene duplication and amplification (GDA). Here we characterise a reversible 33-kb GDA event involving wild-type penA in a CAZ-resistant B. pseudomallei clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 bp) chromosomal sequences, which in this example consist of 4-bp repeats flanked by 3-bp inverted repeats. GDA involving β-lactamases may be a common CAZ resistance mechanism in B. pseudomallei.

KW - Amplification

KW - Burkholderia pseudomallei

KW - Ceftazidime

KW - Gene duplication

KW - Resistance

KW - β-Lactamase

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SN - 0924-8579

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JO - International Journal of Antimicrobial Agents

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ER -

Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification

Abstract

Keywords

ASJC Scopus subject areas

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