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Vitamin K enhances the effect of antibiotics inhibiting the efflux pumps of Staphylococcus aureus strains

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Abstract

The strain Staphylococcus aureus is commonly cited as being a major hospital-acquired pathogen. The emergence of S. aureus strains resistant to a wide distribution of antibiotics. The various antibiotic resistance mechanisms include efflux pumps, are ubiquitous proteins localized in the cytoplasmic membrane of all kind of cells. During the last two decades, numerous structurally diverse compounds have been studied and shown to have efflux-inhibitory activity. These include currently available drugs employed for other indications, as well as natural and synthetic molecules. Menadione (vitamin K3), is a fat-soluble vitamin that has long been recognized for its essential role in coagulation and, more recently, has been proposed as a key nutrient in the regulation of soft tissue calcification. Therefore, the aim of this study is to evaluate the effect of menadione efflux pumps in multidrug resistant strains of S.aureus. Were used RN4220 harboring plasmid pUL5054, which carries the gene encoding the MsrA macrolide efflux protein; and IS-58, which possesses the TetK tetracycline efflux protein; 1199B resists hydrophilic fluoroquinolones via a NorA-mediated mechanism and wild strain 1199B. Antibacterial activity test by minimal inhibitory concentration (MIC). Evaluation of possible inhibition of efflux pumps by reduction of MIC of ethidium bromide (EtBr) and antibiotics due the possible inhibitory effect of these substances. Efforts have been directed at identification of EPIs from natural sources. Some of the detrimental effects on bacterial cells can be attributed to the detergent properties of menadione on account of their amphipathic structure. Was observed what in strain 4220 and IS58 it occurred reduction the MIC, indicating possible effect on efflux pump.

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Author's contributions

SRT, CDMOT, and FFC performed the MIC assays of antibacterial activity of menadione; PWL and PSP performed the efflux Pump Inhibition by MIC Reduction assay; TGS and LJQJ performed the statistical assays; JPSJ, HDMC, TCLB, and VQB supervised the experimental work, wrote and revised the manuscript

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Correspondence to Henrique D. M. Coutinho.

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Tintino, S.R., Oliveira-Tintino, C.D.M., Campina, F.F. et al. Vitamin K enhances the effect of antibiotics inhibiting the efflux pumps of Staphylococcus aureus strains. Med Chem Res 27, 261–267 (2018). https://doi.org/10.1007/s00044-017-2063-y

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