Role for endosomal and vacuolar GTPases in Candida albicans pathogenesis

Douglas A. Johnston, Karen E. Eberle, Joy E. Sturtevant, Glen Palmer

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The vacuole has crucial roles in stress resistance and adaptation of the fungal cell. Furthermore, in Candida albicans it has been observed to undergo dramatic expansion during the initiation of hyphal growth, to produce highly "vacuolated" subapical compartments. We hypothesized that these functions may be crucial for survival within the host and tissue-invasive hyphal growth. We also considered the role of the late endosome or prevacuole compartment (PVC), a distinct organelle involved in vacuolar and endocytic trafficking. We identified two Rab GTPases, encoded by VPS21 and YPT72, required for trafficking through the PVC and vacuole biogenesis, respectively. Deletion of VPS21 or YPT72 led to mild sensitivities to some cellular stresses. However, deletion of both genes resulted in a synthetic phenotype with severe sensitivity to cellular stress and impaired growth. Both the vps21Δ and ypt72Δ mutants had defects in filamentous growth, while the double mutant was completely deficient in polarized growth. The defects in hyphal growth were not suppressed by an "active" RIM101 allele or loss of the hyphal repressor encoded by TUP1. In addition, both single mutants had significant attenuation in a mouse model of hematogenously disseminated candidiasis, while the double mutant was rapidly cleared. Histological examination confirmed that the vps21Δ and ypt72Δ mutants are deficient in hyphal growth in vivo. We suggest that the PVC and vacuole are required on two levels during C. albicans infection: (i) stress resistance functions required for survival within tissue and (ii) a role in filamentous growth which may aid host tissue invasion.

Original languageEnglish (US)
Pages (from-to)2343-2355
Number of pages13
JournalInfection and Immunity
Volume77
Issue number6
DOIs
StatePublished - Jun 1 2009

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GTP Phosphohydrolases
Candida albicans
Growth
Vacuoles
rab GTP-Binding Proteins
Tissue Survival
Candidiasis
Endosomes
Gene Deletion
Organelles
Alleles
Phenotype
Infection

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Role for endosomal and vacuolar GTPases in Candida albicans pathogenesis. / Johnston, Douglas A.; Eberle, Karen E.; Sturtevant, Joy E.; Palmer, Glen.

In: Infection and Immunity, Vol. 77, No. 6, 01.06.2009, p. 2343-2355.

Research output: Contribution to journalArticle

Johnston, Douglas A. ; Eberle, Karen E. ; Sturtevant, Joy E. ; Palmer, Glen. / Role for endosomal and vacuolar GTPases in Candida albicans pathogenesis. In: Infection and Immunity. 2009 ; Vol. 77, No. 6. pp. 2343-2355.
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