Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene

Autores
Ramírez, Ana; Ruggiero, Melina; Aranaga, Carlos; Cataldi, Ángel Adrián; Gutkind, Gabriel Osvaldo; De Waard, Jacobus H.; Araque, María; Power, Pablo
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. BlaMmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. BlaMab and BlaMmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A β-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3′ end of MAB-2874, which may constitute the blaMab and blaMmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of β-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.
Fil: Ramírez, Ana. Universidad de Los Andes; Venezuela
Fil: Ruggiero, Melina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aranaga, Carlos. Instituto Venezolano de Investigaciones Científicas; Venezuela
Fil: Cataldi, Ángel Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias Castelar. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Waard, Jacobus H.. Universidad Central de Venezuela; Venezuela
Fil: Araque, María. Universidad de Los Andes; Venezuela
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Antibiotic Resistance
Mycobacterium Abscessus
Mycobacterium Massiliense
Β-Lactamase
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39356
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/39356
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding geneRamírez, AnaRuggiero, MelinaAranaga, CarlosCataldi, Ángel AdriánGutkind, Gabriel OsvaldoDe Waard, Jacobus H.Araque, MaríaPower, PabloAntibiotic ResistanceMycobacterium AbscessusMycobacterium MassilienseΒ-Lactamasehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. BlaMmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. BlaMab and BlaMmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A β-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3′ end of MAB-2874, which may constitute the blaMab and blaMmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of β-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.Fil: Ramírez, Ana. Universidad de Los Andes; VenezuelaFil: Ruggiero, Melina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aranaga, Carlos. Instituto Venezolano de Investigaciones Científicas; VenezuelaFil: Cataldi, Ángel Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias Castelar. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: De Waard, Jacobus H.. Universidad Central de Venezuela; VenezuelaFil: Araque, María. Universidad de Los Andes; VenezuelaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMary Ann Liebert2017-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39356Ramírez, Ana; Ruggiero, Melina; Aranaga, Carlos; Cataldi, Ángel Adrián; Gutkind, Gabriel Osvaldo; et al.; Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene; Mary Ann Liebert; Microbial Drug Resistance: Mechanisms Epidemiology and Disease; 23; 3; 4-2017; 294-3001076-6294CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1089/mdr.2016.0047info:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/10.1089/mdr.2016.0047info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:13Zoai:ri.conicet.gov.ar:11336/39356instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:13.472CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
title Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
spellingShingle Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
Ramírez, Ana
Antibiotic Resistance
Mycobacterium Abscessus
Mycobacterium Massiliense
Β-Lactamase
title_short Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
title_full Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
title_fullStr Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
title_full_unstemmed Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
title_sort Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene
dc.creator.none.fl_str_mv Ramírez, Ana
Ruggiero, Melina
Aranaga, Carlos
Cataldi, Ángel Adrián
Gutkind, Gabriel Osvaldo
De Waard, Jacobus H.
Araque, María
Power, Pablo
author Ramírez, Ana
author_facet Ramírez, Ana
Ruggiero, Melina
Aranaga, Carlos
Cataldi, Ángel Adrián
Gutkind, Gabriel Osvaldo
De Waard, Jacobus H.
Araque, María
Power, Pablo
author_role author
author2 Ruggiero, Melina
Aranaga, Carlos
Cataldi, Ángel Adrián
Gutkind, Gabriel Osvaldo
De Waard, Jacobus H.
Araque, María
Power, Pablo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antibiotic Resistance
Mycobacterium Abscessus
Mycobacterium Massiliense
Β-Lactamase
topic Antibiotic Resistance
Mycobacterium Abscessus
Mycobacterium Massiliense
Β-Lactamase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. BlaMmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. BlaMab and BlaMmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A β-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3′ end of MAB-2874, which may constitute the blaMab and blaMmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of β-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.
Fil: Ramírez, Ana. Universidad de Los Andes; Venezuela
Fil: Ruggiero, Melina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aranaga, Carlos. Instituto Venezolano de Investigaciones Científicas; Venezuela
Fil: Cataldi, Ángel Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias Castelar. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: De Waard, Jacobus H.. Universidad Central de Venezuela; Venezuela
Fil: Araque, María. Universidad de Los Andes; Venezuela
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The objectives of this study were to determine the kinetic parameters of purified recombinant BlaMab and BlaMmas by spectrophotometry, analyze the genetic environment of the blaMab and blaMmas genes in both species by polymerase chain reaction and sequencing, furthermore, in silico models of both enzymes in complex with imipenem were obtained by modeling tools. Our results showed that BlaMab and BlaMmas have a similar hydrolysis behavior, displaying high catalytic efficiencies toward penams, cephalothin, and nitrocefin; none of the enzymes are well inhibited by clavulanate. BlaMmas hydrolyzes imipenem at higher efficiency than cefotaxime and aztreonam. BlaMab and BlaMmas showed that their closest structural homologs are KPC-2 and SFC-1, which correlate to the mild carbapenemase activity toward imipenem observed at least for BlaMmas. They also seem to differ from other class A β-lactamases by the presence of a more flexible Ω loop, which could impact in the hydrolysis efficiency against some antibiotics. A -35 consensus sequence (TCGACA) and embedded at the 3′ end of MAB-2874, which may constitute the blaMab and blaMmas promoter. Our results suggest that the resistance mechanisms in fast-growing mycobacteria could be probably evolving toward the production of β-lactamases that have improved catalytic efficiencies against some of the drugs commonly used for the treatment of mycobacterial infections, endangering the use of important drugs like the carbapenems.
publishDate 2017
dc.date.none.fl_str_mv 2017-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39356
Ramírez, Ana; Ruggiero, Melina; Aranaga, Carlos; Cataldi, Ángel Adrián; Gutkind, Gabriel Osvaldo; et al.; Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene; Mary Ann Liebert; Microbial Drug Resistance: Mechanisms Epidemiology and Disease; 23; 3; 4-2017; 294-300
1076-6294
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39356
identifier_str_mv Ramírez, Ana; Ruggiero, Melina; Aranaga, Carlos; Cataldi, Ángel Adrián; Gutkind, Gabriel Osvaldo; et al.; Biochemical characterization of β-lactamases from mycobacterium abscessus complex and genetic environment of the β-lactamase-encoding gene; Mary Ann Liebert; Microbial Drug Resistance: Mechanisms Epidemiology and Disease; 23; 3; 4-2017; 294-300
1076-6294
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1089/mdr.2016.0047
info:eu-repo/semantics/altIdentifier/url/https://www.liebertpub.com/doi/10.1089/mdr.2016.0047
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269081298796544
score 13.13397

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