NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate

Autores
Boncompagni, Selene Rebecca; Antonelli, Alberto; Casciato, Benedetta; Pieralli, Filippo; Vila, Alejandro Jose; Moreno, Diego Martin; Giani, Tommaso; Rossolini, Gian Maria
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
NDM-type metallo-β-lactamases (MBLs) are among the most widespread acquired carbapenemases in carbapenem-resistant Enterobacterales. As with other β-lactamases, allelic variability occurs among NDM-type MBLs, with almost 100 variants so far reported, differing by single or multiple amino acid substitutions or insertions, which may have implications for enzymatic activity. In this study, we report on a novel NDM variant, NDM-63, identified in a carbapenem-resistant ST147 Klebsiella pneumoniae from a surveillance rectal swab. Compared to NDM-1, NDM-63 features an original array of changes in the L3 loop, including deletion of phenylalanine at position 70 and two amino acid substitutions (G69S and A72H), due to a four-nucleotide deletion plus a nucleotide insertion in the gene region encoding the L3 loop. When expressed in Escherichia coli under isogenic conditions, NDM-63 conferred a resistance profile overall similar to NDM-1, but exhibiting a lower level of resistance to carbapenems and cefepime, while remaining susceptible to inhibition by taniborbactam. Present findings expand current knowledge on the structural plasticity of NDM-type MBLs and highlight that variability in the L3 loop, which contributes to delimitation of the active site, could also tolerate amino acid deletions without loss of enzymatic activity. A virtually identical K. pneumoniae carrying a non-functional blaNDM allele entailing only the nucleotide insertion observed in blaNDM-63 (which might have played a role in the evolution of blaNDM) was also isolated from a bloodstream infection that occurred in the same patient, yielding a misleading result of molecular diagnostic testing due to the lack of enzyme activity despite the presence of the target gene.
Fil: Boncompagni, Selene Rebecca. University Of Florence; Italia
Fil: Antonelli, Alberto. University Of Florence; Italia
Fil: Casciato, Benedetta. Careggi University Hospital; Italia
Fil: Pieralli, Filippo. University Of Florence; Italia
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Giani, Tommaso. University Of Florence; Italia
Fil: Rossolini, Gian Maria. University Of Florence; Italia
Materia
metallo-β-lactamase
Klebsiella pneumoniae
NDM-63
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:11336/285569
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/285569
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolateBoncompagni, Selene RebeccaAntonelli, AlbertoCasciato, BenedettaPieralli, FilippoVila, Alejandro JoseMoreno, Diego MartinGiani, TommasoRossolini, Gian Mariametallo-β-lactamaseKlebsiella pneumoniaeNDM-63https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1NDM-type metallo-β-lactamases (MBLs) are among the most widespread acquired carbapenemases in carbapenem-resistant Enterobacterales. As with other β-lactamases, allelic variability occurs among NDM-type MBLs, with almost 100 variants so far reported, differing by single or multiple amino acid substitutions or insertions, which may have implications for enzymatic activity. In this study, we report on a novel NDM variant, NDM-63, identified in a carbapenem-resistant ST147 Klebsiella pneumoniae from a surveillance rectal swab. Compared to NDM-1, NDM-63 features an original array of changes in the L3 loop, including deletion of phenylalanine at position 70 and two amino acid substitutions (G69S and A72H), due to a four-nucleotide deletion plus a nucleotide insertion in the gene region encoding the L3 loop. When expressed in Escherichia coli under isogenic conditions, NDM-63 conferred a resistance profile overall similar to NDM-1, but exhibiting a lower level of resistance to carbapenems and cefepime, while remaining susceptible to inhibition by taniborbactam. Present findings expand current knowledge on the structural plasticity of NDM-type MBLs and highlight that variability in the L3 loop, which contributes to delimitation of the active site, could also tolerate amino acid deletions without loss of enzymatic activity. A virtually identical K. pneumoniae carrying a non-functional blaNDM allele entailing only the nucleotide insertion observed in blaNDM-63 (which might have played a role in the evolution of blaNDM) was also isolated from a bloodstream infection that occurred in the same patient, yielding a misleading result of molecular diagnostic testing due to the lack of enzyme activity despite the presence of the target gene.Fil: Boncompagni, Selene Rebecca. University Of Florence; ItaliaFil: Antonelli, Alberto. University Of Florence; ItaliaFil: Casciato, Benedetta. Careggi University Hospital; ItaliaFil: Pieralli, Filippo. University Of Florence; ItaliaFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Giani, Tommaso. University Of Florence; ItaliaFil: Rossolini, Gian Maria. University Of Florence; ItaliaAmerican Society for Microbiology2026-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/285569Boncompagni, Selene Rebecca; Antonelli, Alberto; Casciato, Benedetta; Pieralli, Filippo; Vila, Alejandro Jose; et al.; NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 70; 2; 2-2026; 1-80066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/aac.01286-25info:eu-repo/semantics/altIdentifier/doi/10.1128/aac.01286-25info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:33:15Zoai:ri.conicet.gov.ar:11336/285569instacron: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:34982026-08-25 14:33:15.503CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
title NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
spellingShingle NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
Boncompagni, Selene Rebecca
metallo-β-lactamase
Klebsiella pneumoniae
NDM-63
title_short NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
title_full NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
title_fullStr NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
title_full_unstemmed NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
title_sort NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate
dc.creator.none.fl_str_mv Boncompagni, Selene Rebecca
Antonelli, Alberto
Casciato, Benedetta
Pieralli, Filippo
Vila, Alejandro Jose
Moreno, Diego Martin
Giani, Tommaso
Rossolini, Gian Maria
author Boncompagni, Selene Rebecca
author_facet Boncompagni, Selene Rebecca
Antonelli, Alberto
Casciato, Benedetta
Pieralli, Filippo
Vila, Alejandro Jose
Moreno, Diego Martin
Giani, Tommaso
Rossolini, Gian Maria
author_role author
author2 Antonelli, Alberto
Casciato, Benedetta
Pieralli, Filippo
Vila, Alejandro Jose
Moreno, Diego Martin
Giani, Tommaso
Rossolini, Gian Maria
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv metallo-β-lactamase
Klebsiella pneumoniae
NDM-63
topic metallo-β-lactamase
Klebsiella pneumoniae
NDM-63
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv NDM-type metallo-β-lactamases (MBLs) are among the most widespread acquired carbapenemases in carbapenem-resistant Enterobacterales. As with other β-lactamases, allelic variability occurs among NDM-type MBLs, with almost 100 variants so far reported, differing by single or multiple amino acid substitutions or insertions, which may have implications for enzymatic activity. In this study, we report on a novel NDM variant, NDM-63, identified in a carbapenem-resistant ST147 Klebsiella pneumoniae from a surveillance rectal swab. Compared to NDM-1, NDM-63 features an original array of changes in the L3 loop, including deletion of phenylalanine at position 70 and two amino acid substitutions (G69S and A72H), due to a four-nucleotide deletion plus a nucleotide insertion in the gene region encoding the L3 loop. When expressed in Escherichia coli under isogenic conditions, NDM-63 conferred a resistance profile overall similar to NDM-1, but exhibiting a lower level of resistance to carbapenems and cefepime, while remaining susceptible to inhibition by taniborbactam. Present findings expand current knowledge on the structural plasticity of NDM-type MBLs and highlight that variability in the L3 loop, which contributes to delimitation of the active site, could also tolerate amino acid deletions without loss of enzymatic activity. A virtually identical K. pneumoniae carrying a non-functional blaNDM allele entailing only the nucleotide insertion observed in blaNDM-63 (which might have played a role in the evolution of blaNDM) was also isolated from a bloodstream infection that occurred in the same patient, yielding a misleading result of molecular diagnostic testing due to the lack of enzyme activity despite the presence of the target gene.
Fil: Boncompagni, Selene Rebecca. University Of Florence; Italia
Fil: Antonelli, Alberto. University Of Florence; Italia
Fil: Casciato, Benedetta. Careggi University Hospital; Italia
Fil: Pieralli, Filippo. University Of Florence; Italia
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Moreno, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Giani, Tommaso. University Of Florence; Italia
Fil: Rossolini, Gian Maria. University Of Florence; Italia
description NDM-type metallo-β-lactamases (MBLs) are among the most widespread acquired carbapenemases in carbapenem-resistant Enterobacterales. As with other β-lactamases, allelic variability occurs among NDM-type MBLs, with almost 100 variants so far reported, differing by single or multiple amino acid substitutions or insertions, which may have implications for enzymatic activity. In this study, we report on a novel NDM variant, NDM-63, identified in a carbapenem-resistant ST147 Klebsiella pneumoniae from a surveillance rectal swab. Compared to NDM-1, NDM-63 features an original array of changes in the L3 loop, including deletion of phenylalanine at position 70 and two amino acid substitutions (G69S and A72H), due to a four-nucleotide deletion plus a nucleotide insertion in the gene region encoding the L3 loop. When expressed in Escherichia coli under isogenic conditions, NDM-63 conferred a resistance profile overall similar to NDM-1, but exhibiting a lower level of resistance to carbapenems and cefepime, while remaining susceptible to inhibition by taniborbactam. Present findings expand current knowledge on the structural plasticity of NDM-type MBLs and highlight that variability in the L3 loop, which contributes to delimitation of the active site, could also tolerate amino acid deletions without loss of enzymatic activity. A virtually identical K. pneumoniae carrying a non-functional blaNDM allele entailing only the nucleotide insertion observed in blaNDM-63 (which might have played a role in the evolution of blaNDM) was also isolated from a bloodstream infection that occurred in the same patient, yielding a misleading result of molecular diagnostic testing due to the lack of enzyme activity despite the presence of the target gene.
publishDate 2026
dc.date.none.fl_str_mv 2026-02
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/11336/285569
Boncompagni, Selene Rebecca; Antonelli, Alberto; Casciato, Benedetta; Pieralli, Filippo; Vila, Alejandro Jose; et al.; NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 70; 2; 2-2026; 1-8
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/285569
identifier_str_mv Boncompagni, Selene Rebecca; Antonelli, Alberto; Casciato, Benedetta; Pieralli, Filippo; Vila, Alejandro Jose; et al.; NDM-63: a novel NDM metallo-β-lactamase variant in the L3 loop, from a Klebsiella pneumoniae clinical isolate; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 70; 2; 2-2026; 1-8
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://journals.asm.org/doi/10.1128/aac.01286-25
info:eu-repo/semantics/altIdentifier/doi/10.1128/aac.01286-25
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 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 13.265058

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