Efficacy of Compounds Isolated from <i>Streptomyces olivaceus</i> against the Morphogenesis and Virulence of <i>Candida albicans</i>
Lili Meng | Changli Sun | Chunyan Zhang | Shihao Song | Xiuyun Sun | Jianhua Ju | Yinyue Deng
<i>Candida albicans</i> is a type of commensal fungi which causes serious infections in immunocompromised patients and contributes to high mortality. In the present study, we identified that the extract from <i>Streptomyces olivaceus</i> SCSIO T05 inhibited hypha and biofilm formation of <i>C. albicans</i>. Seven compounds were isolated and evaluated for their effects on the biological functions and virulence of <i>C. albicans</i>. Two leading compounds, compound <b>1</b> (sorbicillin) and compound <b>2</b> (3-methyl-<i>N</i>-(2′-phenethyl)-butyrylamide) were identified as exhibiting strong activity against <i>C. albicans</i> morphological transition, adhesion activity, cytotoxicity, and adhesion to human cells, in a dose-dependent manner. Notably, compound <b>2</b> inhibited <i>C. albicans</i> infection in mouse oral mucosal models. Transcriptomic analysis and real-time PCR results revealed that compound <b>2</b> most likely inhibited the biological functions of <i>C. albicans</i> cells by regulating the expression levels of <i>HWP1</i>, <i>TEC1</i>, <i>ALS1</i>, <i>IFD6</i>, and <i>CSH1</i>, which are associated with filament formation and cell adhesion. Our results suggest that the candidate compounds present excellent efficacy against <i>C. albicans</i> pathogenicity and that they can be developed as potential options for the clinical treatment of candidiasis.
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