Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Response of Candida albicans to taurocholate

ABSTRACT: Presence of taurocholate (TC), a constituent of bile, confers resistance of Candida albicans to antifungals like Caspofungin and Amphotericin B. Transcriptional profiles in presence and absence of TC were compared to determine whether an upregulation of known resistance genes is responsible for this effect. No upregulation was found, and the resistance seemed to be rather based on a direct interaction of TC with the antifungals.

INSTRUMENT(S): GenePix 4000B

ORGANISM(S): Candida albicans

SUBMITTER: Matthias Brock

PROVIDER: E-MTAB-5277 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Encapsulation of Antifungals in Micelles Protects Candida albicans during Gall-Bladder Infection.

Hsieh Shih-Hung SH Brunke Sascha S Brock Matthias M

Frontiers in microbiology 20170201

Candida albicans is a dimorphic fungus that colonizes human mucosal surfaces with the potential to cause life-threatening invasive candidiasis. Studies on systemic candidiasis in a murine infection model using in vivo real-time bioluminescence imaging revealed persistence of C. albicans in the gall bladder under antifungal therapy. Preliminary analyses showed that bile conferred resistance against a wide variety of antifungals enabling survival in this cryptic host niche. He ...[more]

PMID: 28203228

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Project description:Fungal infections are a serious health problem in clinics especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes and echinocandines. Due to emerging resistance to standard therapy and significant side effects and high costs for several antifungals.,there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities we previously screened a compound library, using a new type of activity-selectivity (AS) assay analysing both the antifungal activity and the compatibility with human cells at the same time. One compound, ((S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole (EMC120B12)), showed high antifungal activity against several species of pathogenic yeasts including C. glabrata and C. krusei, species which are highly refractory to antifungals, especially to the commonly used azoles. Here we could show by transcriptional profiling and sterol analysis that the target of this new antifungal compound is the ergosterol pathway. The effects of EMC120B12 on sterol biosynthesis mimic those of fluconazole, strongly indicating that EMC120B12 also targets ERG11 like the azols. But not only the marker sterol 14 methylergosta 8,24(28) dien 3β,6α diol accumulated in C. krusei under EMC120B12 treatment, but also hitherto unknown related sterols. The novel sterols have a 3β,6α diol structure. Furthermore, this is the first time that a benzimidazole structure has been shown to result in a block of the sterol pathway by accumulating marker sterols connected to ERG11 inactivation. In total, three biological replicates were performed. All experiments were performed as dye swaps. Thus, in total 18 arrays have been hybridzed. Hybridization experiments included an untreated reference sample and a sample of cells treated with either ((1S)-1-[1-(3-chlorobenzyl)-1H-benzimidazol-2-yl]-2-methylpropyl-amine) (EMC120B12), Fluconazole or Nocodazole. The array included one technical replicate of each probe.

Dataset Information

Response of Candida albicans to taurocholate

Publications

Encapsulation of Antifungals in Micelles Protects <i>Candida albicans</i> during Gall-Bladder Infection.

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