<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria

ABSTRACT Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acq...

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Autores principales:	Nawarat Somprasong, Carina M. Hall, Jessica R. Webb, Jason W. Sahl, David M. Wagner, Paul Keim, Bart J. Currie, Herbert P. Schweizer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Burkholderia antibiotics resistance efflux pump adaptation β-lactamases Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fec64c1fc3ff41d3a8385935d85b64b4
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spelling	oai:doaj.org-article:fec64c1fc3ff41d3a8385935d85b64b42021-11-15T15:57:01Z<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria10.1128/mBio.00592-202150-7511https://doaj.org/article/fec64c1fc3ff41d3a8385935d85b64b42020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00592-20https://doaj.org/toc/2150-7511ABSTRACT Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB′-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met. IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.Nawarat SomprasongCarina M. HallJessica R. WebbJason W. SahlDavid M. WagnerPaul KeimBart J. CurrieHerbert P. SchweizerAmerican Society for MicrobiologyarticleBurkholderiaantibioticsresistanceefflux pumpadaptationβ-lactamasesMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Burkholderia antibiotics resistance efflux pump adaptation β-lactamases Microbiology QR1-502
spellingShingle	Burkholderia antibiotics resistance efflux pump adaptation β-lactamases Microbiology QR1-502 Nawarat Somprasong Carina M. Hall Jessica R. Webb Jason W. Sahl David M. Wagner Paul Keim Bart J. Currie Herbert P. Schweizer <named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
description	ABSTRACT Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resistant near-neighbor species. Burkholderia ubonensis, a member of the B. cepacia complex (Bcc), is commonly coisolated from environments where B. pseudomallei is present. Unlike B. pseudomallei, in which significant primary carbapenem resistance is rare, it is not uncommon in B. ubonensis, but the underlying mechanisms are unknown. We established that carbapenem resistance in B. ubonensis is due to an inducible class A PenB β-lactamase, as has been shown for other Bcc bacteria. Inducibility is not sufficient for high-level resistance but also requires other determinants, such as a PenB that is more robust than that present in susceptible isolates, as well as other resistance factors. Curiously and diagnostic for the two complexes, both Bpc and Bcc bacteria contain distinct annotated PenA class A β-lactamases. However, the protein from Bcc bacteria is missing its essential active-site serine and, therefore, is not a β-lactamase. Regulated expression of a transcriptional penB′-lacZ (β-galactosidase) fusion in the B. pseudomallei surrogate B. thailandensis confirms that although Bpc bacteria lack an inducible β-lactamase, they contain the components required for responding to aberrant peptidoglycan synthesis resulting from β-lactam challenge. Understanding the diversity of antimicrobial resistance in Burkholderia species is informative about how the challenges arising from potential resistance transfer between them can be met. IMPORTANCE Burkholderia pseudomallei causes melioidosis, a tropical disease that is highly fatal if not properly treated. Our data show that, in contrast to B. pseudomallei, B. ubonensis β-lactam resistance is fundamentally different because intrinsic resistance is mediated by an inducible class A β-lactamase. This includes resistance to carbapenems. Our work demonstrates that studies with near-neighbor species are informative about the diversity of antimicrobial resistance in Burkholderia and can also provide clues about the potential of resistance transfer between bacteria inhabiting the same environment. Knowledge about potential adverse challenges resulting from the horizontal transfer of resistance genes between members of the two complexes enables the design of effective countermeasures.
format	article
author	Nawarat Somprasong Carina M. Hall Jessica R. Webb Jason W. Sahl David M. Wagner Paul Keim Bart J. Currie Herbert P. Schweizer
author_facet	Nawarat Somprasong Carina M. Hall Jessica R. Webb Jason W. Sahl David M. Wagner Paul Keim Bart J. Currie Herbert P. Schweizer
author_sort	Nawarat Somprasong
title	<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
title_short	<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
title_full	<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
title_fullStr	<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
title_full_unstemmed	<named-content content-type="genus-species">Burkholderia ubonensis</named-content> Meropenem Resistance: Insights into Distinct Properties of Class A β-Lactamases in <named-content content-type="genus-species">Burkholderia cepacia</named-content> Complex and <named-content content-type="genus-species">Burkholderia pseudomallei</named-content> Complex Bacteria
title_sort	<named-content content-type="genus-species">burkholderia ubonensis</named-content> meropenem resistance: insights into distinct properties of class a β-lactamases in <named-content content-type="genus-species">burkholderia cepacia</named-content> complex and <named-content content-type="genus-species">burkholderia pseudomallei</named-content> complex bacteria
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/fec64c1fc3ff41d3a8385935d85b64b4
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