Aimee Songo, Hervé Jacquier, Maxime Danjean, Fabrice Compain, Delphine Dorchène, Zainab Edoo, Paul-Louis Woerther, Michel Arthur, David Lebeaux
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引用次数: 0
Abstract
Objective: Molecular determinants of β-lactam resistance are poorly explored for most Nocardia species, such as Nocardia brasiliensis. In this study, we characterized 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 by microdilution for five β-lactam antibiotics associated or not with β-lactamase inhibitors (clavulanate and avibactam, 4µg/mL). Two putative class A β-lactamase encoding genes (blaBRA-1 and blaBRS-1) were identified in the HUJEG-1 genome. Kinetic parameters of purified BRA-1 and BRS-1 were determined by spectrophotometry. Then, we extended the measurement of β-lactam resistance 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 and cephems, but not against penems, suggesting that imipenem resistance was mediated by another mechanism. The hydrolytic activity of BRS-1 was 100- to 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.
Conclusion: N. brasiliensis HUJEG-1 resistance to penams and cephems was mainly due to the class A β-lactamase BRA-1.
期刊介绍：
The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes.
JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR).
Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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