Effect of <i>Streptomyces sp</i> 3400 JX826625 Metabolites on Multidrug Resistant <i>Candida albicans</i> Development and Chemical Characterization of Antifungal Metabolites

Abstract

The search of new antimicrobial metabolites remains until now an alternative to mitigate concerns caused by antimicrobial resistance. This work aims to demonstrate the ability of actinomycete strain (Streptomyces sp 3400 JX826625) to inhibit pathogen yeast growth (Candida albicans), isolated from a woman infected by recidivate candidiasis and to reveal chemical characteristics of the antifungal metabolites produced. Antifungal test using cylinder agar technique showed that the yeast pathogen was resistant to the nystatin 100.000 and the ketoconazole 50 while Streptomyces sp 3400 displayed activity with 25mm of inhibition zone diameter. The optimization of antifungal production parameters by the strain recapitulates that its culture on sporulation agar medium at a pH=5,13, incubated at 30°C for 7 days promoted the activity of the actinomycete; the butanol was the best solvent for antifungal metabolites extraction. Chemical investigation showed that liquid-liquid fractionation method of crude extract allowed to obtain four fractions (hexane, dichloromethane, butanol and aqueous fractions) in which butanol fraction exhibited the best antifungal activity (19mm) according to antifungal test by disk method. Separation of active compounds from this active fraction by TLC method revealed 10 bands and its bioautography showed two active compounds against the pathogen yeast of which the diameters of inhibition zone were 19mm and 10mm, respectively. Chemical screening of the butanolic fraction revealed the presence of terpenes, alkaloids, coumarins and anthracene derivatives family with colorimetry by TLC method. The recovering of active compounds by TLC preparative gave two methanolic fractions (MF1 and MF2) of which MIC and MFC were respectively 1,562µg/ml and 3,625µg/ml for MF1; 17µg/ml and 34µg/ml for MF2. The two compounds were stable in a range of temperature from 19°C to 46°C; however, a best antifungal activity was recorded at-20°C. UV-visible spectra of the two active compounds revealed that Streptomyces sp 3400 contained non-polyene and heptaene group of polyene molecules.