Atividade antimicrobiana de micropartículas contendo Β-Lapachona e Oxima do lapachol em isolados clínicos de Staphylococcus aureus meticilina resistente

Abstract

One Health encompasses areas of knowledge aimed at isolating pathogenic and multi-resistant microorganisms, in addition to seeking therapeutic alternatives for the control and eradication of infectious diseases. Staphylococcus bacteria, in this context, are consider a challenge for human and animal health due to the selection of isolates resistant to antimicrobial therapy. The use and improvement of compounds of natural or synthetic origin have been important for the control of bacterial pathogenicity. The combination of drugs, as well as microencapsulation, are among the strategies for the development of compounds with antimicrobial activity. Thus, the objective of the study was to evaluate the antimicrobial activity of β-lapachone and lapachol Oxima in the suppression of resistance in resistant methicillin Staphylococcus aureus. Initially, a bibliographic survey was carried out regarding the relationship between multidrug resistance and unique health. The determination of the antimicrobial activity of the substances was determined using the microdilution method, in which clinical isolates from humans (n = 3) and animals (n = 7), including ATCC25923, with multidrug resistance characteristics were used. Eudragit® particles containing β-lapachone and lapachol oxime have antimicrobial activity in all isolates. In the synergism test, using the Checkerboard method, there was an increase in the potency of antimicrobials from the analysis of reduction (approximately 96%) of the minimum inhibitory concentration. In the phenotypic interference of the efflux pump, despite the little activity in reducing the minimum inhibitory concentration (MIC) of ethidium bromide, lapachol oxime, in turn, showed the most significant intrinsic activity with the protein (1PW4) free: -91 kJ / mol), than the inhibitor itself, carbonyl cyanide-3-chlorophenylhydrazone, suggesting that its activity has interference with the resistance mechanism. The silica analysis allowed an understanding of the possible mechanism of intermolecular interaction between the substances and the target proteins. Therefore, the study suggests, then, that the MIC reduction of antimicrobials, in synergism, as well as the analysis of phenotypic interference of the efflux pump by the substances, allow to infer the importance of β-lapachone and Lapachol Oxima as promising molecules in the treatment of infections caused by multidrug-resistant microorganisms in the context of One Health.