C16-Fengycin A affect the growth of Candida albicans by destroying its cell wall and accumulating reactive oxygen species

Appl Microbiol Biotechnol. 2019 Nov;103(21-22):8963-8975. doi: 10.1007/s00253-019-10117-5. Epub 2019 Oct 19.

Abstract

Candida albicans is the most common clinical pathogenic fungus, which is highly susceptible to immunodeficiency. Development of novel antifungal agents has become a growing trend in the treatment of Candida infections. C16-Fengycin A, a lipopeptide isolated from Bacillus amyloliquefaciens fmb60 showed significant fungicidal activity against C. albicans. In the study, we explored the possible antifungal mode of C16-Fengycin A. It was predicted that C16-Fengycin A had the ability to disrupt the cell wall due to its alterations of cell ultrastructure, and reduction of cell wall hydrophobicity. This was further confirmed by the changes in the exposure of the cell wall components and down-regulation of the genes related in the cell wall synthesis. Meanwhile, with the treatment of C16-Fengycin A, the levels of reactive oxygen species (ROS) increased, resulting in mitochondrial dysfunction in the cells. We hypothesized that the antifungal mechanism of C16-Fengycin A might be via the destruction of the cell wall and the accumulation of ROS, which could activate the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase (HOG-MAPK) pathway. Our findings indicated that C16-Fengycin A could be a potential antifungal agent that could be used to treat candida infections.

Keywords: Antifungal; Candida albicans; Cell wall; ROS.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Bacillus amyloliquefaciens / metabolism
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Cell Wall / drug effects*
  • Hydrophobic and Hydrophilic Interactions / drug effects
  • Lipopeptides / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Microbial Sensitivity Tests
  • Mitochondria / pathology
  • Reactive Oxygen Species / metabolism*

Substances

  • Antifungal Agents
  • Lipopeptides
  • Reactive Oxygen Species
  • fengycin