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A conserved active site PenA β-lactamase Ambler motif specific for Burkholderia pseudomallei/B. mallei is likely responsible for intrinsic amoxicillin-clavulanic acid sensitivity and facilitates a simple diagnostic PCR assay for melioidosis.

Author(s)
Somprasong N
Hagen JP
Sahl JW
Webb JR
Hall CM
Currie BJ
Wagner DM
Keim P
Schweizer HP
Publication Date
2023-01-12
Abstract
Burkholderia pseudomallei is a soil- and water-dwelling Gram-negative bacterium that causes melioidosis in humans and animals. Amoxicillin-clavulanic acid (AMC) susceptibility has been hailed as an integral part of the screening algorithm for identification of B. pseudomallei, but the molecular basis for the inherent AMC susceptibility of this bacterium remains undefined. This study showed that B. pseudomallei (and the closely-related B. mallei) wild-type strains are the only Burkholderia spp. that contain a (70)STSK(73) PenA Ambler motif. This motif was present in >99.5% of 1820 analysed B. pseudomallei strains and 100% of 83 analysed B. mallei strains, and is proposed as the likely cause for their inherent AMC sensitivity. The authors developed a polymerase chain reaction (PCR) assay that specifically amplifies the penA(70)ST(S/F)K(73)-containing region from B. pseudomallei and B. mallei, but not from the remaining B. pseudomallei complex species or the (70)STFK(73) region from the closely-related penB of B. cepacia complex species. The abundance and purity of the 193-bp PCR fragment from putative B. pseudomallei isolates from clinical and environmental samples is likely sufficient for reliable confirmation of the presence of B. pseudomallei. The PCR assay is designed to be especially suited for use in resource-constrained areas. While not further explored in this study, the assay may allow diagnosis of putative B. mallei in culture isolates from animal and human samples.
Affiliation
The Pathogen and Microbiome Institute, Northern Arizona University, 1395 S Knoles Dr. Flagstaff, AZ 86001-4073, USA.
The Pathogen and Microbiome Institute, Northern Arizona University, 1395 S Knoles Dr. Flagstaff, AZ 86001-4073, USA; Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, USA.
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia; Department of Infectious Diseases and Northern Territory Medical Programme, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
The Pathogen and Microbiome Institute, Northern Arizona University, 1395 S Knoles Dr. Flagstaff, AZ 86001-4073, USA; Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, USA. Electronic address: herbert.schweizer@nau.edu.
Citation
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Int J Antimicrob Agents. 2023 Jan 12;61(3):106714. doi: 10.1016/j.ijantimicag.2023.106714.
Pubmed ID
https://pubmed.ncbi.nlm.nih.gov/36640845/?otool=iaurydwlib
Link
Volume
61
Title
A conserved active site PenA β-lactamase Ambler motif specific for Burkholderia pseudomallei/B. mallei is likely responsible for intrinsic amoxicillin-clavulanic acid sensitivity and facilitates a simple diagnostic PCR assay for melioidosis.
Type of document
Journal Article
Entity Type
Publication

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