Abstract
NDM-1 comprises a carbapenemase that was first detected in 2008 in New Delhi, India. Since then, NDM-1-producing Klebsiella pneumoniae strains have been reported in many countries and usually associated with intra and inter-hospital dissemination, along with travel-related epidemiological links. In South America, Brazil represents the largest reservoir of NMD-1-producing K. pneumoniae. Here, we focused on the detection and molecular/structural characterization of the blaNDM-1 resistance gene/enzyme from 24 K. pneumoniae clinical isolates in the Midwest region of Brazil. Antimicrobial susceptibility assays showed that all isolates are resistant to carbapenems. Molecular typing of the isolates revealed seven clonal groups among the K. pneumoniae isolates, which may indicate intra or inter-hospital dissemination. Moreover, the blaNDM-1 gene was detected in all 24 K. pneumoniae isolates and the full blaNDM-1 gene was cloned. Bioinformatics analysis showed that the NDM-1 enzyme sequence found in our isolates is highly conserved when compared to other NDM-1 enzymes. In addition, molecular docking studies indicate that the NDM-1 identified binds to different carbapenems through hydrogen and zinc coordination bonds. In summary, we present the molecular characterization of NDM-1-producing K. pneumoniae strains isolated from different hospitals, also providing atomic level insights into molecular complexes NDM-1/carbapenem antibiotics.
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Acknowledgements
We thank the Laboratório Central de Saúde Pública (LACEN-DF) for providing the isolates, as well as the Laboratório S-Inova Biotech—Universidade Católica Dom Bosco (UCDB), where the research was carried out. Thanks are also due to CESAM (UID/AMB/50017—POCI-01-0145-FEDER-007638) by FCT/MEC through national funds, to the co-funding by FEDER, within the PT2020 Partnership Agreement and Compete 2020, which supports it. This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT), and Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF).
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Melgarejo, J.L., Cardoso, M.H., Pinto, I.B. et al. Identification, molecular characterization, and structural analysis of the blaNDM-1 gene/enzyme from NDM-1-producing Klebsiella pneumoniae isolates. J Antibiot 72, 155–163 (2019). https://doi.org/10.1038/s41429-018-0126-z
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DOI: https://doi.org/10.1038/s41429-018-0126-z
