Inhibition of Biofilm and Virulence Factors of Candida albicans by Partially Purified Secondary Metabolites of Streptomyces chrestomyceticus Strain ADP4

Current Topics in Medicinal Chemistry
2018.0

Abstract

<jats:sec> <jats:title>Background:</jats:title> <jats:p> Despite several advancements in antifungal drug discovery, fungal diseases like Invasive Candidiasis (IC) still remain associated with high rates of morbidity and mortality worldwide. Thus there is an enormous need for anti-Candida drugs. </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p> The main objectives of the work included: 1. To investigate therapeutically significant classes of secondary metabolites produced by S. chrestomyceticus strain ADP4. 2. To investigate and analyze inhibition of significant virulence attributes of C. albicans, such as, biofilm and secretory hydrolytic enzymes by ADP4 secondary metabolites. 3. Mechanistic analysis of probable compounds for their site of action on Secretary Aspartyl Proteinase 3 (Sap3). </jats:sec> <jats:sec> <jats:title>Methods: </jats:title> <jats:p>Metabolite extract-SDB (MESDB) of S. chrestomyceticus strain ADP4 was fractionated on silica gel column chromatography. Fractions were analyzed for anti-Candida activity by disc diffusion assay. Active fractions were further purified by differential solvent treatment. MIC90 values were determined by broth dilution method. MFC was based on counting viable cells. Inhibition of yeast to hyphae transition and that of production of hydrolytic enzymes were estimated by plate assays. GC-MS of MESDB and Partially Purified Metabolite preparations (PPMs) was done. GRIP docking studies with Sap 3 of C. albicans was done using VLife MDS 4.6 software. </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Chemical profiling showed that ADP4 secondary metabolites contained alkaloids, flavonoids, polyphenols, terpenoids and triterpenes. The MESDB and the PPMs showed low or no cytotoxicity but were able to effectively contain virulence attributes of Candida pathogen. Docking studies revealed that some of the probable compounds have affinity for aspartic acid residue in Sap3 enzyme of C. albicans. </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p> Secondary metabolite of strain ADP4 included important classes of therapeutically important compounds. Their anti-Candida activity was mediated by inhibition of critical virulence factors of the pathogen. </jats:sec>

Knowledge Graph

Similar Paper

Inhibition of Biofilm and Virulence Factors of Candida albicans by Partially Purified Secondary Metabolites of Streptomyces chrestomyceticus Strain ADP4
Current Topics in Medicinal Chemistry 2018.0
Efficacy of Compounds Isolated from Streptomyces olivaceus against the Morphogenesis and Virulence of Candida albicans
Marine Drugs 2019.0
Polyketide Glycosides from <i>Bionectria ochroleuca</i> Inhibit <i>Candida albicans</i> Biofilm Formation
Journal of Natural Products 2014.0
Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors
European Journal of Medicinal Chemistry 2020.0
Waikialoid A Suppresses Hyphal Morphogenesis and Inhibits Biofilm Development in Pathogenic <i>Candida albicans</i>
Journal of Natural Products 2012.0
Waikialoid A Suppresses Hyphal Morphogenesis and Inhibits Biofilm Development in Pathogenic <i>Candida albicans</i>
Journal of Natural Products 2012.0
Identification of Inhibitors of Drug-Resistant Candida albicans Strains from a Library of Bicyclic Peptidomimetic Compounds
Journal of Medicinal Chemistry 2010.0
Tetracycline-Inducible Expression of Individual Secreted Aspartic Proteases in Candida albicans Allows Isoenzyme-Specific Inhibitor Screening
Antimicrobial Agents and Chemotherapy 2008.0
Study on the inhibitory effect of fermentation extract of Microporus vernicipes on Candida albicans
International Microbiology 2023.0
Polycyclic tetrahydroxanthones from Streptomyces chrestomyceticus BCC 24770
Tetrahedron 2016.0