Endosomal trafficking defects can induce calcium-dependent azole tolerance in Candida albicans

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The azole antifungals arrest fungal growth through inhibition of ergosterol biosynthesis. We recently reported that a Candida albicans vps21 Δ/Δ mutant, deficient in membrane trafficking through the late endosome/prevacuolar compartment (PVC), continues to grow in the presence of the azoles despite the depletion of cellular ergosterol. Here, we report that the vps21 Δ/Δ mutant exhibits less plasma membrane damage upon azole treatment than the wild type, as measured by the release of a cytoplasmic luciferase reporter into the culture supernatant. Our results also reveal that the vps21 Δ/Δ mutant has abnormal levels of intracellular Ca2+ and, in the presence of fluconazole, enhanced expression of a calcineurin-responsive RTA2-GFP reporter. Furthermore, the azole tolerance phenotype of the vps21 Δ/Δ mutant is dependent upon both extracellular calcium levels and calcineurin activity. These findings underscore the importance of endosomal trafficking in determining the cellular consequences of azole treatment and indicate that this may occur through modulation of calcium- and calcineurin-dependent responses.

Original languageEnglish (US)
Pages (from-to)7170-7177
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Azoles
Candida albicans
Calcineurin
Calcium
Ergosterol
Fluconazole
Endosomes
Luciferases
Cell Membrane
Phenotype
Membranes
Growth

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Endosomal trafficking defects can induce calcium-dependent azole tolerance in Candida albicans. / Luna Tapia, Arturo; Tournu, Helene; Peters, Tracy L.; Palmer, Glen.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 12, 01.12.2016, p. 7170-7177.

Research output: Contribution to journalArticle

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