Background: Efflux pumps are transmembrane proteins that expel drugs out of a bacterial cell contributing to microorganism drug resistance. Several studies addressing the use of natural products with medicinal properties have intensified given the above. Thus, the aim of the present study was to investigate the antibacterial activity and the O-eugenol potential in resistance reversal by efflux pump inhibition, as well as to evaluate its toxicity in the arthropod model. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the O-eugenol efflux pump inhibition. For the toxicity assays, mortality and locomotor system damage were performed using the fumigation method.
Results: O-eugenol presented a MIC of 1024 g/mL against . The association of this compound with the antibiotic tetracycline demonstrated a synergistic effect ( < 0.0001), this also being observed when the antibiotic was associated with ethidium bromide ( < 0.0001); thus, these results may be attributable to an efflux pump inhibition. The mortality and geotaxis assays revealed the compound is toxic, with an EC of 18 g/mL within 48 hours of exposure.
Conclusions: While we can conclude that the tested product has an efflux pump inhibitory effect, further studies are needed to elucidate its mechanisms of action, in addition to assays using other strains to verify whether the substance has the same inhibitory effect.
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http://dx.doi.org/10.1155/2022/1440996 | DOI Listing |
Front Microbiol
January 2025
Service of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
Antibiotic-resistant Gram-negative bacteria are an increasing threat to human health. Strategies to restore antibiotic efficacy include targeting multidrug efflux pumps by competitive efflux pump inhibitors. These could be derived from natural substrates of these efflux systems.
View Article and Find Full Text PDFNPJ Antimicrob Resist
August 2024
Biofilm Research Group, School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK.
Multidrug efflux pumps have been found to play a crucial role in drug resistance in bacteria and eukaryotes. In this study, we investigated the presence of functional multidrug and toxic compound extrusion (MATE) efflux pumps, inferred from whole genome sequencing, in the halophilic archaeon Halorubrum amylolyticum CSM52 using Hoechst 33342 dye accumulation and antimicrobial sensitivity tests in the presence and absence of efflux pump inhibitors (EPIs). The whole genome sequence of H.
View Article and Find Full Text PDFNPJ Antimicrob Resist
March 2024
Computational Biology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Gram-negative bacteria cause the majority of critically drug-resistant infections, necessitating the rapid development of new drugs with Gram-negative activity. However, drug design is hampered by the low permeability of the Gram-negative cell envelope and the function of drug efflux pumps, which extrude foreign molecules from the cell. A better understanding of the molecular determinants of compound recognition by efflux pumps is, therefore, essential.
View Article and Find Full Text PDFChemMedChem
January 2025
University of Perugia: Universita degli Studi di Perugia, Department of Pharmaceutical Sciences, ITALY.
In this study, we analyzed publicly accessible data related to the Staphylococcus aureus NorA protein, a well-known efflux pump involved in antimicrobial resistance. Our analysis revealed several inconsistencies in data annotation, and significant issues concerning the homogeneity across datasets, which compromise the reliability of data-driven approaches aimed at identifying novel Staphylococcus aureus NorA efflux pump inhibitors (EPIs). To address these challenges, we propose a standardized pipeline for experimental procedures and data annotation, designed to enhance the consistency and quality of EPI datasets submitted to repositories, thereby increasing the utility of publicly available datasets for the discovery of potential EPIs.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Tigecycline (Tgc), a third-generation tetracycline is found as the last line of defense against multi-drug resistant bacteria. Recent increased rate of resistance to tgc, a human-restricted agent among animal bacteria poses a significant global health challenge. Overuse of first generation tetracyclines (Tet) and phenicols in animals have been suggested to be associated with Tgc resistance development.
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