Biosynthesis of ergosterol



Keywords: biosynthesis of ergosterol
Description: The aim of this work was to evaluate the anti- Candida efficacy of twenty five molecules of plant origin. Based on their MICs, effective molecules were categorized into four categories.

The aim of this work was to evaluate the anti-Candida efficacy of twenty five molecules of plant origin. Based on their MICs, effective molecules were categorized into four categories. Susceptibility testing of test compounds was carried out by standard methodology (M27-A2) as per CLSI guidelines. Minimum Fungicidal Concentration (MFC) was determined as the lowest concentration of drug killing 99.9% cells. Effect on sterol profile was evaluated by sterol quantitation method. Among the screened molecules, cinnamaldehyde, piperidine, citral, furfuraldehyde and indole were potent inhibitors of growth and viability. Exposure of Candida cells to cinnamaldehyde, piperidine, citral, furfuraldehyde, indole, α- and β- pinene at MIC’s, altered ergosterol profile. Our results indicate that the molecules altering sterol profile may exert their antifungal effect through inhibition of ergosterol biosynthesis and could be good candidates for fungal specific drug development.

Candida albicans is a predominant organism associated with candidiasis and can lead to severe diseases which range from superficial infections to life threatening systemic disorders (Kaleli et al. 2007 ). Candida species are now recognized as a major cause of hospital-acquired infections (Maschmeyer 2006 ; Berman & Sudbery 2002 ). Most of the drugs available to treat Candida infections target the ergosterol biosynthetic pathway or its end product ergosterol. The antifungal agents which target ergosterol include azoles, allylamines, thiocarbamates, polyenes and morpholines (Sanglard et al. 2003 ). Most of the antifungals have severe hepatotoxicity, nephrotoxicity and in addition human pathogenic fungi have also developed resistance (Cannon et al. 2009 ; Odds et al. 2003 ; Gupta & Thomas 2003 ). The high toxicity and multiple drug resistance associated with various standard antifungals have necessitated the search for safer alternatives.

In recent years, secondary metabolites have been extensively investigated as sources of medicinal agents (Michal & Klaus 2009 ). Molecules of natural origin (e.g. plants) are known to possess good antifungal potential (Cowan 1999 ) and may efficiently target various biosynthetic pathways like ergosterol synthesis. Essential oils as well as their components have been shown to exert anti-Candida activities (Zore et al. 2010 ,2011 ; Devkatte at al. 2005 ). Small molecules such as carvacrol, thymol, eugenol and epigallocatechin-3-gallate (EGCG) are reported to inhibit ergosterol biosynthesis in C. albicans (Ahmed et al. 2011 ; Ahmad et al. 2010 ; Navarro-Martinez et al. 2006 ).

In this communication we report the anti-Candida properties of twenty five small molecules of plant origin.

Majority of the molecules were found to be effective and showed considerable inhibition of growth at very low concentration. On the basis of MIC achieved against C. albicans ATCC 90028, molecules could be classified into four classes. Molecules, showing MIC at 0.0625-0.5 mg/ml concentration are classified as most effective (ME). Molecules with an MIC ranging from 1 to 2 mg/ml are included in the moderately effective (MoE) group. Molecules with an MIC of 2 to 4 mg/ml are considered as less effective (LE). While, molecules which did not show MIC up to highest concentration tested (i.e. 8 mg/ml) are non effective (NE) (Table ​ (Table1 1 ).






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