Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms.

Autor: Leitão AC; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Ferreira TL; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Gurgel do Amaral Valente Sá L; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.; Christus University Center, Fortaleza, CE, Brazil., Rodrigues DS; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., de Souza BO; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Barbosa AD; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Moreira LEA; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., de Andrade Neto JB; Christus University Center, Fortaleza, CE, Brazil., Cabral VPF; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Rios MEF; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Cavalcanti BC; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Silva J; Department of Chemistry, Theoretical Chemistry and Electrochemistry Group (GQTE), State University of Ceará, Limoeiro do Norte, CE, Brazil., Marinho ES; Department of Chemistry, Theoretical Chemistry and Electrochemistry Group (GQTE), State University of Ceará, Limoeiro do Norte, CE, Brazil., Dos Santos HS; Center for Exact Sciences and Technology, Acaraú Valley State University, Sobral, CE, Brazil., de Moraes MO; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Júnior HVN; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., da Silva CR; Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory for Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Drug Research & Development Center, Federal University of Ceará, Fortaleza, CE, Brazil.
Jazyk: angličtina
Zdroj: Journal of medical microbiology [J Med Microbiol] 2023 Sep; Vol. 72 (9).
DOI: 10.1099/jmm.0.001751
Abstrakt: Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml -1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.
Databáze: MEDLINE