Efeito antimicrobiano do composto 2- Feniletinil-butiltelurio em cepas de Escherichia coli e sua associação com o estresse oxidativo

Abstract

The indiscriminate use of antibiotics causes some bacterial strains to develop defenses against antibacterial agents, with the consequent appearance of antimicrobial resistance. Bacteria such as Escherichia coli, which are present in the microbial flora of individuals, have shown a significant increase in resistance to antibiotics, and along with this increase of resistance comes the search for new drugs to combat these resistant microorganisms. Organic tellurium compounds have shown antimicrobial ability against strains of Gram-negative and Gram-positive bacteria. This class of compounds have these effects related to the oxidation of thiols groups. In this way, the objective of this work was to verify the antimicrobial activity of 2-phenylethynyl butyltelurium (PEBT) in strains of E. coli, as well as, to study if the antimicrobial action is related to its pro-oxidant effect. For the evaluation of the antimicrobial activity of the PEBT the following tests were performed: Disc diffusion with PEBT at the concentrations of 1.28; 0.128; 0.0128 and 0.00128 mg/disc; minimum inhibitory concentration (MIC) with PEBT at concentrations of 3.84; 1.92; 0.96; 0.48; 0.24; 0.12; 0.06 and 0.030 mg/ml; and survival curve, with PEBT at concentrations of 0.96; 1.92 and 3.84 mg/ml (corresponding to 0.5MIC, MIC and 2MIC, respectively). To evaluate if the antimicrobial action is related to its pro-oxidant effect we carried out the levels of extracellular reactive species (RS); activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and levels of non-protein thiols (NPSH). In order to confirm its pro-oxidant effect, the antioxidants glutathione (GSH) and ascorbic acid (AA) were added to the culture medium. Our study has demonstrated that PEBT has antimicrobial capability at concentrations of 1.28 and 0.128 mg/disc by formation of inhibition halo in the diffusion disc test. Additionally, the lowest concentration of the compound capable of inhibiting bacterial growth was 1.92 mg/ml, and in the survival curve test the compound was able to cause bacterial cell infeasibility after the 9 hour exposure time at the concentrations of 0.96; 1.92 and 3.84mg/ml. Our results in biochemical analysis show that the presence of the PEBT at concentrations of 3.84; 1.92 and 0.96mg/ml is able to induce an increase in extracellular RS production in E. coli cells, concomitant with a decrease in intracellular thiol levels and a reduction in the activity of antioxidant enzymes SOD and CAT. Associated with these results, the addiction of GSH and AA to the medium was able to protect the bacterial cell from the antimicrobial effect of PEBT, by disappearance of the inhibition halo in the disc 11 diffusion test. Taken together, our results suggest that the PEBT presents antimicrobial activity against strains of E. coli and its action is related to the generation of RS, oxidation of thiol groups and decrease of the antioxidant defenses of the bacterial cell.