Peptides from Galleria mellonella against Cryptococcus spp: toxicity in three-dimensional cell cultures and G. mellonella

Future Microbiol. 2025 Jan;20(1):11-21. doi: 10.1080/17460913.2024.2421632. Epub 2024 Nov 18.

Abstract

Aim: This work aimed to test peptides against the planktonic and biofilm form of Cryptococcus spp. and in vitro toxicity using three-dimensional (3D) cells characterized and evaluate in vivo toxicity in Galleria mellonella.Materials & methods: Susceptibility tests were conducted on the planktonic form and biofilm formation. The toxicity of the peptides was evaluated in lung and brain cells in monolayer (2D) and 3D mono- and co-culture, in addition to in vivo analysis with G. mellonella.Results: Susceptibility values ranged from 31.25 to over 250 µg/ml with a fungicidal profile. Regarding toxicity, the PepM2 peptide was not toxic in 3D culture (500 µg/ml). G. mellonella, showed a survival rate of more than 85% In assays with brain and lung cell lines, concentrations ranged from 4 × 104 to 4 × 103 cells/well for brain cells and 1 × 103 cells/well for lung cells. Cocultures used 1 × 105 brain and 1 × 103 lung cells.Conclusion: This study shows that the peptides have great potential against cryptococcosis, and all spheroids were characterized as having a spheroidal and compact structure.

Keywords: Galleria mellonella; antifungal; biofilm; cryptococcosis; lung coculture; three-dimensional culture.

Plain language summary

[Box: see text].

MeSH terms

  • Animals
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / toxicity
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Brain / drug effects
  • Cell Culture Techniques, Three Dimensional / methods
  • Cell Line
  • Coculture Techniques
  • Cryptococcosis* / microbiology
  • Cryptococcus* / drug effects
  • Humans
  • Larva / drug effects
  • Larva / microbiology
  • Microbial Sensitivity Tests*
  • Moths* / drug effects
  • Moths* / microbiology
  • Peptides / chemistry
  • Peptides / pharmacology
  • Peptides / toxicity

Substances

  • Antifungal Agents
  • Peptides