A fungal pH-responsive signaling pathway regulating Aspergillus adaptation and invasion into the cornea

Xia Hua1, Xiaoyong Yuan, Kirk R Wilhelmus

  • 1Sid W Richardson Ocular Microbiology Laboratory, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

Insights

Mutations in palB and pacC genes of Aspergillus nidulans attenuated fungal invasion of the cornea. The PacC pathway is crucial for regulating fungal filamentation during corneal infections.

Area of Science:

  • Mycology
  • Pathogenesis
  • Molecular Biology

Background:

  • Aspergillus nidulans is a fungus that can cause opportunistic infections.
  • pH-responsive pathways are essential for fungal adaptation and virulence.
  • The PalB and PacC proteins are components of a pH-sensing system in A. nidulans.

Purpose of the Study:

  • To investigate the role of PalB and PacC in the pathogenesis of Aspergillus nidulans corneal infections.
  • To determine how these pH-responsive pathway components affect fungal invasion and filamentation in the cornea.

Main Methods:

  • Utilized wild-type, palB, and pacC loss-of-function mutants of A. nidulans.
  • Assessed fungal growth kinetics in vitro under varying pH conditions.
  • Evaluated corneal virulence ex vivo using scarified porcine and human corneas.

Main Results:

  • palB and pacC mutants showed significantly reduced hyphal invasion of corneal stroma compared to wild-type A. nidulans.
  • In vitro growth rates were similar in liquid media but the pacC mutant exhibited slower growth on solid media.
  • Reconstituted strains restored virulence to wild-type levels, confirming gene function.

Conclusions:

  • palB and pacC mutant strains of A. nidulans exhibit attenuated corneal invasion.
  • The PacC pathway plays a significant role in regulating fungal filamentation during Aspergillus corneal infections.
  • Targeting this pathway could offer strategies for treating fungal keratitis.

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