Inhibition of Staphylococcus aureus Efflux Pump by O‐Eugenol and Its Toxicity in Drosophila melanogaster Animal Model

Abstract

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 Staphylococcus aureus resistance reversal by efflux pump inhibition, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the O-eugenol efflux pump inhibition. For the D. melanogaster toxicity assays, mortality and locomotor system damage were performed using the fumigation method. Results. O-eugenol presented a MIC of 1024 μg/mL against S. aureus. The association of this compound with the antibiotic tetracycline demonstrated a synergistic effect ( p < 0.0001 ), this also being observed when the antibiotic was associated with ethidium bromide ( p < 0.0001 ); thus, these results may be attributable to an efflux pump inhibition. The D. melanogaster mortality and geotaxis assays revealed the compound is toxic, with an EC50 of 18 μg/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.

Achievement of the Selectivity of Cytotoxic Agents against Cancer Cells by Creation of Combined Formulation with Terpenoid Adjuvants as Prospects to Overcome Multidrug Resistance

“…For EG and its analogues, anti-inflammatory, analgesic, and antimicrobial action have been shown; moreover, EG is a synergist of antibiotics [29,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In the aspect of antitumor activity about EG, it is known that this safe substance is comparable in strength to toxic cisplatin on some types of cells (e.g., U-937, HL-60, HepG2, 3LL Lewis, SNU-C5-IC 50 is from 20 to 130 µM) [49].…”

The Major Facilitator Superfamily and Antimicrobial Resistance Efflux Pumps of the ESKAPEE Pathogen Staphylococcus aureus

“…TetA(K) was one of the first MFS efflux pumps characterized in S. aureus [158]. In a study on MRSA strains, the tetracycline MIC was reduced 3 to 16 times with eugenol as an EPI [159]. Many other terpinenes are reported to be inhibitors of the Tet(K) efflux pump, such as the monoterpene α-pinene [160,161] and the combination of α-terpinene with essential oil from Chenopodium ambrosioides [162].…”

Triphenylphosphine Derivatives of Allylbenzenes Express Antitumor and Adjuvant Activity When Solubilized with Cyclodextrin-Based Formulations

“…Modern therapeutic strategies are in some cases ineffective against bacterial infections and cancers, with such cases being most often associated with multiple drug resistance (MDR) [1][2][3][4][5][6][7][8][9][10][11]. Resistance mechanisms that reduce the likelihood of a patient's being cured can be divided into two groups [12]: (i) cellular metabolism (transferases, topoisomerases, growth factors), which alters the mechanism of action of the drugs or interferes with their action, and (ii) a decrease in the intracellular concentration of the drug.…”

“…Thus, the individual components of essential oils and their modifications are potential candidates for empowered medicinal combinations. However, such substances are often lipophilic [2,11,19,25,27,50,58,[61][62][63][64], which makes it difficult to use them in medical practice, so the adjuvant should be used in a molecular container, such as liposomes or a polymeric carrier. Cyclodextrins (CDs) [23,31,32,[65][66][67][68][69][70][71][72][73][74][75][76] or polycations/polyanions (chitosan, polyethyleneimine, pectin, alginate, heparin, etc.)…”