Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam

Autores
Ghiglione, Barbara; Rodríguez, María Margarita; Brunetti, Florencia Lourdes; Papp Wallace, Krisztina M.; Yoshizumi, Ayumi; Ishii, Yoshikazu; Bonomo, Robert A.; Gutkind, Gabriel Osvaldo; Klinke, Sebastian; Power, Pablo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described. Recently, a variant named CTX-M-151 was isolated from a Salmonella enterica subsp. enterica serovar Choleraesuis strain in Japan. This variant possesses a low degree of amino acid identity with the other CTX-Ms (63.2% to 69.7% with respect to the mature proteins), and thus it may represent a new subgroup within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (inactivation rate [kinact]/inhibition constant [Ki] = 0.15μM-1 · s-1). For AVI, the apparent inhibition constant (Ki app), 0.4mM, was comparable to that of KPC-2; the acylation rate (k2/K) (37,000 M-1 · s-1) was lower than that for CTX-M-15, while the deacylation rate (koff) (0.0015 s21) was 2- to 14-fold higher than those of other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points toward Ser130, which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference toward cefotaxime (CTX) and ceftriaxone (CRO) to that toward ceftazidime (CAZ).
Fil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Rodríguez, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
Fil: Brunetti, Florencia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
Fil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados Unidos
Fil: Yoshizumi, Ayumi. Toho University; Japón
Fil: Ishii, Yoshikazu. Toho University; Japón
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
Materia
CEFOTAXIMASE
DBO
ESBL
PHYLOGENY
SALMONELLA CHOLERAESUIS
X-RAY CRYSTALLOGRAPHY
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:11336/140876
Acceder
id CONICETDig_d603d12d9642f9ce03030e887751017c
oai_identifier_str oai:ri.conicet.gov.ar:11336/140876
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactamGhiglione, BarbaraRodríguez, María MargaritaBrunetti, Florencia LourdesPapp Wallace, Krisztina M.Yoshizumi, AyumiIshii, YoshikazuBonomo, Robert A.Gutkind, Gabriel OsvaldoKlinke, SebastianPower, PabloCEFOTAXIMASEDBOESBLPHYLOGENYSALMONELLA CHOLERAESUISX-RAY CRYSTALLOGRAPHYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described. Recently, a variant named CTX-M-151 was isolated from a Salmonella enterica subsp. enterica serovar Choleraesuis strain in Japan. This variant possesses a low degree of amino acid identity with the other CTX-Ms (63.2% to 69.7% with respect to the mature proteins), and thus it may represent a new subgroup within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (inactivation rate [kinact]/inhibition constant [Ki] = 0.15μM-1 · s-1). For AVI, the apparent inhibition constant (Ki app), 0.4mM, was comparable to that of KPC-2; the acylation rate (k2/K) (37,000 M-1 · s-1) was lower than that for CTX-M-15, while the deacylation rate (koff) (0.0015 s21) was 2- to 14-fold higher than those of other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points toward Ser130, which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference toward cefotaxime (CTX) and ceftriaxone (CRO) to that toward ceftazidime (CAZ).Fil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Rodríguez, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Brunetti, Florencia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados UnidosFil: Yoshizumi, Ayumi. Toho University; JapónFil: Ishii, Yoshikazu. Toho University; JapónFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaAmerican Society for Microbiology2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/140876Ghiglione, Barbara; Rodríguez, María Margarita; Brunetti, Florencia Lourdes; Papp Wallace, Krisztina M.; Yoshizumi, Ayumi; et al.; Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 4; 4-2021; 1-140066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aac.asm.org/content/65/4/e01757-20info:eu-repo/semantics/altIdentifier/doi/10.1128/aac.01757-20info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:47Zoai:ri.conicet.gov.ar:11336/140876instacron: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 09:43:48.125CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
title Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
spellingShingle Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
Ghiglione, Barbara
CEFOTAXIMASE
DBO
ESBL
PHYLOGENY
SALMONELLA CHOLERAESUIS
X-RAY CRYSTALLOGRAPHY
title_short Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
title_full Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
title_fullStr Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
title_full_unstemmed Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
title_sort Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam
dc.creator.none.fl_str_mv Ghiglione, Barbara
Rodríguez, María Margarita
Brunetti, Florencia Lourdes
Papp Wallace, Krisztina M.
Yoshizumi, Ayumi
Ishii, Yoshikazu
Bonomo, Robert A.
Gutkind, Gabriel Osvaldo
Klinke, Sebastian
Power, Pablo
author Ghiglione, Barbara
author_facet Ghiglione, Barbara
Rodríguez, María Margarita
Brunetti, Florencia Lourdes
Papp Wallace, Krisztina M.
Yoshizumi, Ayumi
Ishii, Yoshikazu
Bonomo, Robert A.
Gutkind, Gabriel Osvaldo
Klinke, Sebastian
Power, Pablo
author_role author
author2 Rodríguez, María Margarita
Brunetti, Florencia Lourdes
Papp Wallace, Krisztina M.
Yoshizumi, Ayumi
Ishii, Yoshikazu
Bonomo, Robert A.
Gutkind, Gabriel Osvaldo
Klinke, Sebastian
Power, Pablo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CEFOTAXIMASE
DBO
ESBL
PHYLOGENY
SALMONELLA CHOLERAESUIS
X-RAY CRYSTALLOGRAPHY
topic CEFOTAXIMASE
DBO
ESBL
PHYLOGENY
SALMONELLA CHOLERAESUIS
X-RAY CRYSTALLOGRAPHY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described. Recently, a variant named CTX-M-151 was isolated from a Salmonella enterica subsp. enterica serovar Choleraesuis strain in Japan. This variant possesses a low degree of amino acid identity with the other CTX-Ms (63.2% to 69.7% with respect to the mature proteins), and thus it may represent a new subgroup within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (inactivation rate [kinact]/inhibition constant [Ki] = 0.15μM-1 · s-1). For AVI, the apparent inhibition constant (Ki app), 0.4mM, was comparable to that of KPC-2; the acylation rate (k2/K) (37,000 M-1 · s-1) was lower than that for CTX-M-15, while the deacylation rate (koff) (0.0015 s21) was 2- to 14-fold higher than those of other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points toward Ser130, which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference toward cefotaxime (CTX) and ceftriaxone (CRO) to that toward ceftazidime (CAZ).
Fil: Ghiglione, Barbara. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Rodríguez, María Margarita. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
Fil: Brunetti, Florencia Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
Fil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados Unidos
Fil: Yoshizumi, Ayumi. Toho University; Japón
Fil: Ishii, Yoshikazu. Toho University; Japón
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
Fil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina
description The diazabicyclooctane (DBO) inhibitor avibactam (AVI) reversibly inactivates most serine β-lactamases, including the CTX-M β-lactamases. Currently, more than 230 unique CTX-M members distributed in five clusters with less than 5% amino acid sequence divergence within each group have been described. Recently, a variant named CTX-M-151 was isolated from a Salmonella enterica subsp. enterica serovar Choleraesuis strain in Japan. This variant possesses a low degree of amino acid identity with the other CTX-Ms (63.2% to 69.7% with respect to the mature proteins), and thus it may represent a new subgroup within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (inactivation rate [kinact]/inhibition constant [Ki] = 0.15μM-1 · s-1). For AVI, the apparent inhibition constant (Ki app), 0.4mM, was comparable to that of KPC-2; the acylation rate (k2/K) (37,000 M-1 · s-1) was lower than that for CTX-M-15, while the deacylation rate (koff) (0.0015 s21) was 2- to 14-fold higher than those of other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points toward Ser130, which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference toward cefotaxime (CTX) and ceftriaxone (CRO) to that toward ceftazidime (CAZ).
publishDate 2021
dc.date.none.fl_str_mv 2021-04
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/11336/140876
Ghiglione, Barbara; Rodríguez, María Margarita; Brunetti, Florencia Lourdes; Papp Wallace, Krisztina M.; Yoshizumi, Ayumi; et al.; Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 4; 4-2021; 1-14
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/140876
identifier_str_mv Ghiglione, Barbara; Rodríguez, María Margarita; Brunetti, Florencia Lourdes; Papp Wallace, Krisztina M.; Yoshizumi, Ayumi; et al.; Structural and biochemical characterization of the novel CTXM-151 extended-spectrum β-lactamase and its inhibition by avibactam; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 4; 4-2021; 1-14
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://aac.asm.org/content/65/4/e01757-20
info:eu-repo/semantics/altIdentifier/doi/10.1128/aac.01757-20
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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
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score 13.13397

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