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Transcriptome Study of an Exophiala dermatitidis PKS1 Mutant on an ex Vivo Skin Model: Is Melanin Important for

Caroline Poyntner1, Ursula Mirastschijski2,3, Katja Sterflinger1

  • 1Department of Biotechnology, VIBT EQ Extremophile Center, University of Natural Resources and Life Sciences, Vienna, Austria.

Frontiers in Microbiology
|July 19, 2018
PubMed

Insights

Melanin significantly enhances the invasiveness and virulence of the human pathogen Exophiala dermatitidis during skin infections. A melanin-deficient mutant showed reduced colonization and no invasiveness compared to the wild-type fungus.

Area of Science:

  • Medical Mycology
  • Pathogen Biology
  • Fungal Genetics

Background:

  • Exophiala dermatitidis is a polyextremophilic yeast causing human infections.
  • Increasing cases of E. dermatitidis infections occur in both immunocompromised and immunocompetent individuals.
  • Knowledge of E. dermatitidis infection mechanisms and virulence factors is limited.

Purpose of the Study:

  • To investigate the role of melanin, a putative virulence factor, in E. dermatitidis skin infections.
  • To compare the invasive potential of wild-type and melanin-deficient E. dermatitidis strains on human skin.

Main Methods:

  • Generated a melanin-deficient mutant of E. dermatitidis using CRISPR/Cas9 targeting the PKS1 gene.
  • Utilized an ex vivo skin organ culture model to simulate cutaneous infection with wild-type and mutant strains.
  • Performed whole RNA-sequencing to analyze transcriptional differences between strains.

Main Results:

  • The melanin-deficient mutant exhibited reduced skin colonization and lacked invasiveness compared to the wild-type.
  • Wild-type E. dermatitidis fully colonized the stratum corneum, invaded the skin, and infected keratinocytes within seven days.
  • Transcriptional analysis revealed minor differences in pathways related to copper homeostasis, cell wall genes, and proteases.

Conclusions:

  • Melanin plays a critical role in the early stages of E. dermatitidis skin infection, significantly enhancing fungal invasiveness and virulence.
  • Targeting melanin production could be a potential strategy to combat E. dermatitidis infections.
Keywords:
Exophiala dermatitidisPKS1black yeastmelaninskin modelvirulence

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