Burkholderia pseudomallei acquired ceftazidime resistance due to gene duplication and amplification.
Chirakul S., Somprasong N., Norris MH., Wuthiekanun V., Chantratita N., Tuanyok A., Schweizer HP.
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.