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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/27978
Title: Molecular basis of rare aminoglycoside susceptibility and pathogenesis of Burkholderia pseudomalleiclinical isolates from Thailand
Authors: Lily A. Trunck
Katie L. Propst
Vanaporn Wuthiekanun
Apichai Tuanyok
Stephen M. Beckstrom-Sternberg
James S. Beckstrom-Sternberg
Sharon J. Peacock
Paul Keim
Steven W. Dow
Herbert P. Schweizer
Colorado State University
Mahidol University
Northern Arizona University
Translational Genomics Research Institute
University of Cambridge
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Sep-2009
Citation: PLoS Neglected Tropical Diseases. Vol.3, No.9 (2009)
Abstract: Background: Burkholderia pseudomallei is intrinsically resistant to aminoglycosides and macrolides, mostly due to AmrAB-OprA efflux pump expression. We investigated the molecular mechanisms of aminoglycoside susceptibility exhibited by Thai strains 708a, 2188a, and 3799a. Methodology/Principal Findings:qRT-PCR revealed absence of amrB transcripts in 708a and greatly reduced levels in 2188a and 3799a. Serial passage on increasing gentamicin concentrations yielded 2188a and 3799a mutants that became simultaneously resistant to other aminoglycosides and macrolides, whereas such mutants could not be obtained with 708a. Transcript analysis showed that the resistance of the 2188a and 3799a mutants was due to upregulation of amrAB-oprA expression by unknown mechanism(s). Use of a PCR walking strategy revealed that the amrAB-oprA operon was missing in 708a and that this loss was associated with deletion of more than 70 kb of genetic material. Rescue of the amrAB-oprB region from a 708a fosmid library and sequencing showed the presence of a large chromosome 1 deletion (131 kb and 141 kb compared to strains K96243 and 1710b, respectively). This deletion not only removed the amrAB-oprA operon, but also the entire gene clusters for malleobactin and cobalamin synthesis. Other genes deleted included the anaerobic arginine deiminase pathway, putative type 1 fimbriae and secreted chitinase. Whole genome sequencing and PCR analysis confirmed absence of these genes from708a. Despite missing several putative virulence genes, 708a was fully virulent in amurine melioidosismodel. Conclusions/Significance: Strain 708a may be a natural candidate for genetic manipulation experiments that use Select Agent compliant antibiotics for selection and validates the use of laboratory-constructed Δ(amrAB-oprA) mutants in such experiments. © 2009 Trunck et al.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=70449504714&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/27978
Appears in Collections:Scopus 2006-2010

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