TY - JOUR
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.
N1 - Funding Information:
This work was supported by University of Florida Preeminence Initiative start-up funds to HPS. AT was supported by CRDF Global Grant # OISE-9531011 . The sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Funding Information:
This work was supported by University of Florida Preeminence Initiative start-up funds to HPS. AT was supported by CRDF Global Grant # OISE-9531011. The sponsors had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© 2019 Elsevier Ltd
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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U2 - 10.1016/j.ijantimicag.2019.01.003
DO - 10.1016/j.ijantimicag.2019.01.003
M3 - Article
C2 - 30639528
AN - SCOPUS:85061932818
SN - 0924-8579
VL - 53
SP - 582
EP - 588
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 5
ER -