Ceftazidime is the antibiotic of choice for treatment of Burkholderia pseudomallei infections (melioidosis). The chromosomally encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant ceftazidime resistance only when overexpressed due to a promoter mutation, transcriptional anti-termination or by gene duplication and amplification (GDA). Here we characterize a reversible 33-kb GDA event involving wild-type penA in a ceftazidime resistant clinical isolate from Thailand. We show that duplication arises from exchanges between short (<10 base pairs, bp) chromosomal sequences, which in this example consist of 4 bp repeats flanked by 3 bp inverted repeats. GDA involving β-lactamase may be a common ceftazidime resistance mechanism in B. pseudomallei.
International journal of antimicrobial agents
Department of Molecular Genetics and Microbiology, College of Medicine, Emerging Pathogens Institute, Institute for Therapeutic Innovation, University of Florida, Gainesville, FL, USA.