Journal
LIFE SCIENCES
Volume 285, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119940
Keywords
Isoeugenol; Staphylococcus aureus; Efflux pump; Phenylpropene; Alternative method; Natural product
Funding
- Cearense Foundation for the Support of Scientific and Technological Development -FUNCAP [BP3-013900077.01.00/18, BP4-0172-00168.01.00/20, 09673071/2020]
- Geopark Araripe
- National Council for Scientific and Technological Development -CNPq
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This study evaluated the ability of isoeugenol to inhibit Staphylococcus aureus efflux pumps and its toxicity against a eukaryotic model (Drosophila melanogaster). Isoeugenol showed antibacterial and synergistic effects when combined with antibiotics, while also demonstrating acute toxicity against D. melanogaster.
The Staphylococcus aureus bacteria is a pathogen considered opportunistic and that has been acquiring resistance to several classes of antibiotics, mainly due to the synthesis of efflux pumps, which are proteins that expel these drugs intracellularly, reducing their effectiveness. The objective of this study was to evaluate the ability of isoeugenol to inhibit S. aureus efflux pumps and to determine its toxicity against a eukaryotic model (Drosophila melanogaster). IS-58, K2068 and K4414 S. aureus strains were used in the study. Isoeugenol minimum inhibitory concentration (MIC) and antibiotic modulation were evaluated in efflux pump inhibitory tests as well as in ethidium bromide (EtBr) assays. Toxicity tests against D. melanogaster assessed mortality and negative geotaxis. Isoeugenol obtained a relevant MIC result and a synergism was observed when isoeugenol was associated with the antibiotics, mainly with ciprofloxacin. Isoeugenol was able to affect all three efflux pumps tested, especially in strain K4414. The mortality of D. melanogaster caused by isoeugenol administration started after 12 h of exposure, being volume dependent and having an LC50 of 81.69 ILL/L. In the negative geotaxis test, a statistical difference was observed after 24h of exposure compared to the control, demonstrating that damage to the locomotor apparatus had occurred. Based on the results, isoeugenol is a putative efflux pump inhibitor, becoming an alternative in blocking these proteins, and demonstrated acute toxicity against D. melanogaster.
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