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An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
07:42

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract

Published on: July 1, 2020

Endosomal and AP-3-dependent vacuolar trafficking routes make additive contributions to Candida albicans hyphal

Glen E Palmer1

  • 1Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, 70119, USA. gpalme@lsuhsc.edu

Eukaryotic Cell
|September 28, 2010
PubMed

Insights

Candida albicans hyphal growth and virulence depend on vacuolar trafficking pathways. Disrupting both the AP-3 (Aps3p) and endosomal (Vps21p) routes severely impairs hyphal formation and reduces virulence.

Area of Science:

  • Mycology
  • Cell Biology
  • Molecular Pathogenesis

Background:

  • Vacuolar biogenesis is crucial for Candida albicans hyphal growth and virulence.
  • Two Golgi-to-vacuole trafficking routes exist in Saccharomyces cerevisiae: one endosomal (Vps21p-dependent) and one bypassing the endosome (AP-3 complex-dependent, including Aps3p).
  • The specific roles of these distinct vacuolar trafficking pathways in C. albicans hyphal development and pathogenicity remain unclear.

Purpose of the Study:

  • To investigate the significance of the Vps21p-dependent and AP-3 complex-dependent vacuolar trafficking pathways in C. albicans hyphal growth.
  • To determine the contribution of these pathways to C. albicans virulence in a murine model.
  • To elucidate the interplay between these two trafficking routes.

Main Methods:

  • Construction and phenotypic analysis of C. albicans aps3Δ/Δ, vps21Δ/Δ, and aps3Δ/Δ vps21Δ/Δ mutant strains.
  • Assessment of vacuolar morphology and localization of vacuolar proteins (e.g., Mlt1p).
  • Evaluation of hyphal growth defects and virulence in a mouse model of disseminated candidiasis.

Main Results:

  • C. albicans Aps3p and Vps21p mediate distinct vacuolar transport pathways.
  • The vps21Δ/Δ mutant showed minor defects in hyphal elongation, while the aps3Δ/Δ mutant exhibited no hyphal growth defect.
  • The aps3Δ/Δ vps21Δ/Δ double mutant displayed severely reduced hyphal growth, forming pseudohyphae lacking vacuolated compartments.
  • The aps3Δ/Δ strain was virulent, vps21Δ/Δ persisted in kidneys, and the double mutant was avirulent and cleared.
  • Ume6p-induced hyphal growth and subapical vacuolation were observed, but the double mutant failed to form these structures.

Conclusions:

  • The AP-3 pathway (Aps3p) has a limited role in C. albicans hyphal growth and virulence independently.
  • The Vps21p-dependent endosomal pathway is important for hyphal elongation and virulence.
  • Disruption of both pathways synergistically impairs hyphal formation and abrogates virulence, highlighting the critical role of coordinated vacuolar trafficking.
  • The AP-3 pathway becomes significantly important when endosomal trafficking is compromised.

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