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Eugenol as a synergistic adjuvant to conventional antibiotics against multidrug-resistant Klebsiella pneumoniae: An integrated in vitro and quantum-based in silico approach

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de Barros, Amanda Vieira ; de Veras, Bruno Oliveira ; Menezes, Gabriela de Lima ; Bezerra, Katyanna Sales ; dos Santos, Patryck Ermerson Monteiro ; de Sa, Rafael Artur De Queiroz Cavalcanti ; Fulco, Umberto Laino ; Galvao, Douglas Soares ; Paiva, Patricia Maria Guedes ; Malafaia, Guilherme ; da Silva, Marcia Vanusa ; Coutinho, Henrique Douglas Melo ; de Oliveira, Maria Betania Melo
Número total de Autores: 13
Tipo de documento: Artigo Científico
Fonte: Microbial Pathogenesis; v. 210, p. 13-pg., 2025-10-27.
Resumo

The escalating antimicrobial resistance of Klebsiella pneumoniae poses a critical public health challenge, demanding innovative therapeutic strategies. This study investigated the antibacterial activity of eugenol (EOL) and its potential as a resistance-modulating agent when combined with conventional antibiotics-amoxicillin (AXL), azithromycin (AZT), cephalexin (CEF), and ciprofloxacin (CIP)-against clinical multidrug-resistant isolates. EOL exhibited intrinsic antibacterial activity with MIC values ranging from 1024 to 2048 mu g/mL. Checkerboard assays revealed synergistic interactions between EOL and AXL or AZT (FICI <= 0.5), while combinations with CEF and CIP were indifferent. These synergistic effects were corroborated by growth inhibition curves, time-kill kinetics, and biofilm suppression assays, all of which demonstrated a marked reduction in bacterial viability and biofilm formation. Molecular docking and quantum mechanical calculations further elucidated the enhanced binding affinities and intermolecular interactions between AXL-EOL complexes and key resistance-related targets (KPC, LpxC, and particularly the quorum-sensing regulator SdiA), with interaction energies reaching up to-52.06 kcal/mol. Altogether, the findings underscore the potential of EOL as a potent adjuvant that augments the efficacy of conventional antibiotics, offering a promising pathway toward the development of targeted therapies against multidrug-resistant K. pneumoniae. (AU)

Processo FAPESP: 13/08293-7 - CECC - Centro de Engenharia e Ciências Computacionais
Beneficiário:Munir Salomao Skaf
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs