Affiliation:
1. Université Côte d’Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), Nice, France
Abstract
ABSTRACT
Ergosterol, an essential plasma membrane amphipathic lipid, is a major component of the fungal plasma membrane. Most fungal pathogens are susceptible to azole drugs that target ergosterol biosynthesis, and resistance/tolerance to azoles is increasingly problematic.
Candida albicans
is the most prevalent etiology of candidiasis, and, in this fungal pathogen, ergosterol-rich sub-domains are likely to include sphingolipids, as well as specific membrane proteins, such as multidrug transporters. To investigate the dynamics of ergosterol during the cell cycle and whether drug treatment affects these dynamics in this opportunistic pathogen, we adapted the D4H (domain 4 of the perfringolysin O bacterial toxin) reporter for studying sterol-rich membrane domains. We show that D4H provides a direct readout for the cellular effects of fluconazole and that highly polarized ergosterol is not critical for budding or filamentous growth.
IMPORTANCE
Ergosterol is a critical membrane lipid in fungi. In
Candida albicans
, this essential plasma membrane amphipathic lipid is important for interactions with host cells, in particular, host immune responses. Here, we use a live-cell reporter for specifically visualizing ergosterol and show that apical enrichment of this sterol is not critical for budding and filamentous growth in this human fungal pathogen. Our results highlight that this live-cell reporter is likely to be a useful tool in the analyses of azole resistance and tolerance mechanisms, including alterations in drug targets and upregulation of efflux activities.
Funder
Agence Nationale de la Recherche
European Commission
EC | European Research Council
Centre National de la Recherche Scientifique
Institut National de la Santé et de la Recherche Médicale
Université Côte d'Azur
Publisher
American Society for Microbiology
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献