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Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis.
Antimicrob Agents Chemother. 2017 06; 61(6)AA

Abstract

Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis.

Authors+Show Affiliations

Centers for Disease Control and Prevention, Atlanta, Georgia, USA jbugrysheva@cdc.gov.Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Centers for Disease Control and Prevention, Atlanta, Georgia, USA.Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.Department of Molecular Genetics and Microbiology, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28396541

Citation

Bugrysheva, Julia V., et al. "Antibiotic Resistance Markers in Burkholderia Pseudomallei Strain Bp1651 Identified By Genome Sequence Analysis." Antimicrobial Agents and Chemotherapy, vol. 61, no. 6, 2017.
Bugrysheva JV, Sue D, Gee JE, et al. Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis. Antimicrob Agents Chemother. 2017;61(6).
Bugrysheva, J. V., Sue, D., Gee, J. E., Elrod, M. G., Hoffmaster, A. R., Randall, L. B., Chirakul, S., Tuanyok, A., Schweizer, H. P., & Weigel, L. M. (2017). Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis. Antimicrobial Agents and Chemotherapy, 61(6). https://doi.org/10.1128/AAC.00010-17
Bugrysheva JV, et al. Antibiotic Resistance Markers in Burkholderia Pseudomallei Strain Bp1651 Identified By Genome Sequence Analysis. Antimicrob Agents Chemother. 2017;61(6) PubMed PMID: 28396541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibiotic Resistance Markers in Burkholderia pseudomallei Strain Bp1651 Identified by Genome Sequence Analysis. AU - Bugrysheva,Julia V, AU - Sue,David, AU - Gee,Jay E, AU - Elrod,Mindy G, AU - Hoffmaster,Alex R, AU - Randall,Linnell B, AU - Chirakul,Sunisa, AU - Tuanyok,Apichai, AU - Schweizer,Herbert P, AU - Weigel,Linda M, Y1 - 2017/05/24/ PY - 2017/01/08/received PY - 2017/03/31/accepted PY - 2017/4/12/pubmed PY - 2018/2/27/medline PY - 2017/4/12/entrez KW - Burkholderia pseudomallei KW - antimicrobial resistance KW - genome sequence KW - penA JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 61 IS - 6 N2 - Burkholderia pseudomallei Bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). We sequenced, assembled, and annotated the Bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicly available antimicrobial resistance prediction tools, and published reports. More than 100 genes in the Bp1651 sequence were identified as potentially contributing to antimicrobial resistance. Most notably, we identified three previously uncharacterized point mutations in penA, which codes for a class A β-lactamase and was previously implicated in resistance to β-lactam antibiotics. The mutations result in amino acid changes T147A, D240G, and V261I. When individually introduced into select agent-excluded B. pseudomallei strain Bp82, D240G was found to contribute to ceftazidime resistance and T147A contributed to amoxicillin-clavulanic acid and imipenem resistance. This study provides the first evidence that mutations in penA may alter susceptibility to carbapenems in B. pseudomallei Another mutation of interest was a point mutation affecting the dihydrofolate reductase gene folA, which likely explains the trimethoprim resistance of this strain. Bp1651 was susceptible to aminoglycosides likely because of a frameshift in the amrB gene, the transporter subunit of the AmrAB-OprA efflux pump. These findings expand the role of penA to include resistance to carbapenems and may assist in the development of molecular diagnostics that predict antimicrobial resistance and provide guidance for treatment of melioidosis. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/28396541/Antibiotic_Resistance_Markers_in_Burkholderia_pseudomallei_Strain_Bp1651_Identified_by_Genome_Sequence_Analysis_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=28396541 DB - PRIME DP - Unbound Medicine ER -