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 journalArticlepeer-review

10 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 languageEnglish (US)
Pages (from-to)582-588
Number of pages7
JournalInternational Journal of Antimicrobial Agents
Volume53
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

Keywords

  • Amplification
  • Burkholderia pseudomallei
  • Ceftazidime
  • Gene duplication
  • Resistance
  • β-Lactamase

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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