Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics
ABSTRACT: Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine...
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Elsevier
2025-05-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716525000335 |
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| author | Aimee Songo Hervé Jacquier Maxime Danjean Fabrice Compain Delphine Dorchène Zainab Edoo Paul-Louis Woerther Michel Arthur David Lebeaux |
| author_facet | Aimee Songo Hervé Jacquier Maxime Danjean Fabrice Compain Delphine Dorchène Zainab Edoo Paul-Louis Woerther Michel Arthur David Lebeaux |
| author_sort | Aimee Songo |
| collection | DOAJ |
| description | ABSTRACT: Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N. brasiliensis clinical strains. Methods: The susceptibility of N. brasiliensis HUJEG-1 was determined by measuring the MIC via microdilution for five β-lactam antibiotics that were or were not associated with β-lactamase inhibitors (clavulanate and avibactam, 4 µg/mL). Two putative class A β-lactamase-encoding genes (blaBRA-1 and blaBRS-1) were identified in the HUJEG-1 genome. The kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Measurement of β-lactam resistance was then extended to nine clinical strains. These phenotypic data were compared with the genomic diversity of whole genomes (next-generation sequencing). Results: N. brasiliensis HUJEG-1 was resistant to amoxicillin, cefuroxime, and cefotaxime, but susceptible to their combination with clavulanate or avibactam. This strain was resistant to imipenem (with or without inhibitors) and susceptible to meropenem. BRA-1 showed high catalytic efficiencies against penams (penicillin, ampicillin) and cephems (cephaloridine, cephalothin, and cefamandole), but not against penems (imipenem, meropenem), suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100–1000-fold lower than that of BRA-1 for all β-lactams tested, suggesting that BRS-1 has a minor contribution to β-lactam resistance. Analysis of the nine clinical strains showed variations in susceptibility to cefotaxime, as well as diversity in genetic backgrounds and BRA-1 sequences. Conclusions: N. brasiliensis HUJEG-1 resistance to penams and cephems is mainly due to the class A β-lactamase BRA-1. |
| format | Article |
| id | doaj-art-2f9fe1ed6adf44cbbd8ff6c05bfe7f5a |
| institution | OA Journals |
| issn | 2213-7165 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-2f9fe1ed6adf44cbbd8ff6c05bfe7f5a2025-08-20T02:27:06ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-05-014213514110.1016/j.jgar.2025.01.022Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibioticsAimee Songo0Hervé Jacquier1Maxime Danjean2Fabrice Compain3Delphine Dorchène4Zainab Edoo5Paul-Louis Woerther6Michel Arthur7David Lebeaux8Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, FranceEA DYNAMYC 7380, Faculté de Santé, Université Paris-Est Créteil, Créteil, France; Unité de Bactériologie, Département de Prévention, Diagnostic et Traitement des Infections, APHP, GHU Henri Mondor, Créteil, FranceEA DYNAMYC 7380, Faculté de Santé, Université Paris-Est Créteil, Créteil, France; Unité de Bactériologie, Département de Prévention, Diagnostic et Traitement des Infections, APHP, GHU Henri Mondor, Créteil, FranceCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, FranceCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, FranceCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, FranceEA DYNAMYC 7380, Faculté de Santé, Université Paris-Est Créteil, Créteil, France; Unité de Bactériologie, Département de Prévention, Diagnostic et Traitement des Infections, APHP, GHU Henri Mondor, Créteil, FranceCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, FranceCentre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, U1138, LRMA, Equipe 12, Paris, France; Université Paris Cité, Paris, France; Service de Microbiologie, Unité Mobile d'Infectiologie, APHP, Hôpital Européen Georges Pompidou, Paris, France; Corresponding author. Mailing address: LRMA, Équipe 12, Centre de Recherche des Cordeliers, 15 rue de l’École de Médecine, 75006 Paris, France.ABSTRACT: Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterised resistance mediated by two β-lactamases in the reference strain N. brasiliensis HUJEG-1 and extended our analysis to nine N. brasiliensis clinical strains. Methods: The susceptibility of N. brasiliensis HUJEG-1 was determined by measuring the MIC via microdilution for five β-lactam antibiotics that were or were not associated with β-lactamase inhibitors (clavulanate and avibactam, 4 µg/mL). Two putative class A β-lactamase-encoding genes (blaBRA-1 and blaBRS-1) were identified in the HUJEG-1 genome. The kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Measurement of β-lactam resistance was then extended to nine clinical strains. These phenotypic data were compared with the genomic diversity of whole genomes (next-generation sequencing). Results: N. brasiliensis HUJEG-1 was resistant to amoxicillin, cefuroxime, and cefotaxime, but susceptible to their combination with clavulanate or avibactam. This strain was resistant to imipenem (with or without inhibitors) and susceptible to meropenem. BRA-1 showed high catalytic efficiencies against penams (penicillin, ampicillin) and cephems (cephaloridine, cephalothin, and cefamandole), but not against penems (imipenem, meropenem), suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100–1000-fold lower than that of BRA-1 for all β-lactams tested, suggesting that BRS-1 has a minor contribution to β-lactam resistance. Analysis of the nine clinical strains showed variations in susceptibility to cefotaxime, as well as diversity in genetic backgrounds and BRA-1 sequences. Conclusions: N. brasiliensis HUJEG-1 resistance to penams and cephems is mainly due to the class A β-lactamase BRA-1.http://www.sciencedirect.com/science/article/pii/S2213716525000335Nocardia brasiliensisβ-lactam resistanceClass Aβ-lactamaseBRA-1BRS-1 |
| spellingShingle | Aimee Songo Hervé Jacquier Maxime Danjean Fabrice Compain Delphine Dorchène Zainab Edoo Paul-Louis Woerther Michel Arthur David Lebeaux Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics Journal of Global Antimicrobial Resistance Nocardia brasiliensis β-lactam resistance Class A β-lactamase BRA-1 BRS-1 |
| title | Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics |
| title_full | Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics |
| title_fullStr | Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics |
| title_full_unstemmed | Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics |
| title_short | Analysis of two Nocardia brasiliensis class A β-lactamases (BRA-1 and BRS-1) and related resistance to β-lactam antibiotics |
| title_sort | analysis of two nocardia brasiliensis class a β lactamases bra 1 and brs 1 and related resistance to β lactam antibiotics |
| topic | Nocardia brasiliensis β-lactam resistance Class A β-lactamase BRA-1 BRS-1 |
| url | http://www.sciencedirect.com/science/article/pii/S2213716525000335 |
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