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.

Highlights

  • Resistance to antimicrobials becomes nowadays a main concern of health sector and the entire world

  • Antifungal drugs commonly used to treat Candida albicans infections are azoles, echinocandines and polyenes but recently, most of them were shown to be inactive against the target yeast [5]

  • The present work aims to assess the effect of secondary metabolites produced by Streptomyces sp 3400 JX826625 isolated from ginger rhizospheric soil [9, 10] on multidrug resistant Candida albicans

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Summary

Introduction

Resistance to antimicrobials becomes nowadays a main concern of health sector and the entire world. Several factors can be implied in antifungal resistance that can be either intrinsic or acquired, among others, the repetitive use of the antifungal drugs in immunocompromised patients [6] and the interaction with antibacterial medications [7] This situation requires urgently the necessity to find out novel antifungal molecules and the use of microorganisms from unexplored or rarely explored site is an alternative. Work researches in actinomycetes isolated from different ecological niches pay yet researchers’ attention in the hope to discover novel secondary metabolites to fight against recurrent diseases due to antimicrobial resistance This microorganism group is selected in this study for their ability to produce diverse types of secondary metabolites with different biological activities. Optimization of antifungal production parameters and chemical aspects of antifungal metabolites are reported

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