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Int J Antimicrob Agents. 2019 Jun 4. pii: S0924-8579(19)30133-5. doi: 10.1016/j.ijantimicag.2019.05.016. [Epub ahead of print]

Aripiprazole repurposed as an inhibitor of biofilm formation, and sterol biosynthesis in multi-drug resistant Candida albicans.

Author information

1
School of Chemical Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea.
2
School of Chemical Engineering, Yeungnam University, Gyeongsan, 38541, Republic of Korea. Electronic address: jtlee@ynu.ac.kr.

Abstract

Drug repurposing is an anticipative chemotherapeutic strategy that serves to accentuate the inadequacy of antifungal drugs. The study identifies an antipsychotic drug, aripiprazole, as a biofilm and hyphal inhibitor of Candida albicans. Microtitre plate biofilm inhibition, metabolic activity, and hyphal inhibitory assays were used initially to assess the potency of aripiprazole, while assays like filipin staining, reactive oxygen species staining, cAMP rescue, propidium iodide staining, computational studies, and qRT-PCR assays were used to elucidate its mode of action. The study revealed aripiprazole functioned in a manner similar to standard azoles, especially the imidazole ketoconazole, by inhibiting pseudohyphal formations during the early stages of hyphal development. The action of aripiprazole on C. albicans was dose-dependent and it exhibited varied action mechanisms at low and high dosages. At low dosage, aripiprazole outperformed ketoconazole in terms of inhibiting biofilm formation, hyphal filamentations, and yeast flocculation whereas at higher dosage it mimicked ketoconazole. In conclusion, the study illustrates the anti-candidal potential and mechanistic activities of aripiprazole, and suggests the future use of this drug as an anti-biofilm agent.

KEYWORDS:

Aripiprazole; Azoles; Biofilm; C. albicans; Ergosterol; Filipin

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