An Erg11 lanosterol 14-α-demethylase-Arv1 complex is required for Candida albicans virulence

PloS One
Michelle L VillasmilJoseph Nickels

Abstract

Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important to identify new drug targets for drug discovery and novel therapeutics. Arv1 (are1 are2 required for viability 1) function is highly conserved between multiple pathogenic fungal species. Candida albicans (C. albicans) cells lacking CaArv1 are azole hypersusceptible and lack virulence. Saccharomyces cerevisiae (S. cerevisiae) Scarv1 cells are also azole hypersusceptible, a phenotype reversed by expression of CaArv1, indicating conservation in the molecular mechanism for azole susceptibility. To define the relationship between Arv1 function and azole susceptibility, we undertook a structure/function analysis of ScArv1. We identified several conserved amino acids within the ScArv1 homology domain (ScAhd) required for maintaining normal azole susceptibility. Erg11 lanosterol 14-α-demethylase is the rate-limiting enzyme in sterol biosynthesis and is the direct target of azole antifungals, so we used our ScArv1 mutants in order to explore the relationship between ScArv1 and ScErg11. Specific ScArv1 mutants ectopically expressed from a low copy plasmid...Continue Reading

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Citations

Dec 3, 2020·Journal of Microbiology and Biotechnology·Lingmei Sun, Kai Liao

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Methods Mentioned

BETA
ubiquitination
fluorescence microscopy
deubiquitination
two-hybrid
co-immunoprecipitation
pull down
PCR
Co-IP
chip
fluorescence imaging

Software Mentioned

ImageJ
Zeiss ZEN2
Adobe Photoshop
Volocity

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