Development of carbazole derivatives compounds against candida albicans: Candidates to prevent hyphal formation via the Ras1‐MAPK pathway

Young Kwang Park, Jisoo Shin, Hee Yoon Lee, Hag Dong Kim, Joon Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Morphogenesis contributes to the virulence of the opportunistic human fungal pathogen Candida albicans. Ras1‐MAPK pathways play a critical role in the virulence of C. albicans by regulating cell growth, morphogenesis, and biofilm formation. Ume6 acts as a transcription factor, and Nrg1 is a transcriptional repressor for the expression of hyphal‐specific genes in morphogenesis. Azoles or echinocandin drugs have been extensively prescribed for C. albicans infections, which has led to the development of drug‐resistant strains. Therefore, it is necessary to develop new molecules to effectively treat fungal infections. Here, we showed that Molecule B and Molecule C, which contained a carbazole structure, attenuated the pathogenicity of C. albicans through inhibition of the Ras1/MAPK pathway. We found that Molecule B and Molecule C inhibit morphogenesis through repressing protein and RNA levels of Ras/MAPK‐related genes, including UME6 and NRG1. Furthermore, we determined the antifungal effects of Molecule B and Molecule C in vivo using a candidiasis murine model. We anticipate our findings are that Molecule B and Molecule C, which inhibits the Ras1/MAPK pathway, are promising compounds for the development of new antifungal agents for the treatment of systemic candidiasis and possibly for other fungal diseases.

Original languageEnglish
Article number688
JournalJournal of Fungi
Volume7
Issue number9
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • Biofilm formation
  • Candida albicans
  • Candidiasis
  • Drug development
  • Drug resistance
  • Fungi
  • MAPK pathway
  • Morphogenesis
  • Pathogenicity
  • Ras1

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Plant Science
  • Microbiology (medical)

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