Galleria mellonella immune melanization is fungicidal during infection

Daniel F Q Smith1, Quigly Dragotakes1, Madhura Kulkarni1

  • 1W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.

Communications Biology
|December 12, 2022
PubMed

Insights

Insect immune response involves melanin production. This study shows melanin encapsulation directly kills fungi like Cryptococcus neoformans and Candida albicans in Galleria mellonella, acting as a key antifungal defense.

Area of Science:

  • * Insect immunology
  • * Fungal pathogenesis
  • * Biochemistry

Background:

  • * Melanin production is a crucial insect immune response, forming nodules around microbes.
  • * Melanization generates toxic intermediates, but its direct fungicidal role remains unproven.
  • * Previous work showed Cryptococcus neoformans encapsulated in melanin nodules in Galleria mellonella.

Purpose of the Study:

  • * To investigate the direct fungicidal role of melanin during fungal infections in vivo.
  • * To develop and apply advanced techniques for studying immune melanization.
  • * To explore the impact of fungal morphology on melanization response.

Main Methods:

  • * Developed tissue-clearing techniques for in situ visualization of melanized nodules.
  • * Established a time-lapse microscopy protocol to analyze melanization kinetics in hemolymph.
  • * Investigated responses to Cryptococcus neoformans, Candida albicans, and Candida auris.

Main Results:

  • * Demonstrated that in vivo melanin encapsulation is fungicidal against C. neoformans.
  • * Identified fungal melanin and laccase as enhancers of immune melanization.
  • * Observed that yeast forms of C. albicans and C. auris elicit strong melanization, while hyphal forms evade it.
  • * Found that approximately 23% of encapsulated C. albicans yeast can survive and escape.

Conclusions:

  • * Immune melanization serves as a direct antifungal mechanism in G. mellonella.
  • * Melanin encapsulation effectively inhibits fungal growth and survival.
  • * Fungal morphology significantly influences the efficacy of the melanization response.