Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Mar 23;22(1):foac019. doi: 10.1093/femsyr/foac019

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

PMC Copyright notice

Figure 1. — Effect of antifungal drugs (I), resistance mechanisms against antifungals (II) and the effect of resistance on virulence (III). Azoles inhibit the ergosterol biosynthesis in fungi, which leads to toxic sterol accumulation (I-A). Resistance against azoles can occur via efflux pump overexpression by transportation of drug molecules out of the cell (II-A/1), via ERG3 loss-of-function (LOF) mutation leading to decreased toxic sterol production (II-A/2) or via mutation/overexpression of ERG11 (II-A/3). The effect of overexpression of efflux pumps on the virulence is controversial as it caused increased virulence in C. glabrata and C. parapsilosis fluconazole-resistant strains but led to the reduction of virulence in C. tropicalis and voriconazole-resistant C. parapsilosis strains in mice model (III-A/1). In most of the studies, ERG3 LOF mutation caused decreased virulence in posaconazole-resistant C. parapsilosis and C. albicans strains; however, in some special cases erg3 mutant C. albicans isolates showed increased virulence in mice (III-A/2). Overexpression and point mutation in ERG11 caused decreased virulence in C. auris isolates (III-A/3). Echinocandins block β-glucan synthesis by inhibiting the Fks1p glucan-synthase subunit (I-B). Resistance to echinocandins can occur via point mutations in the FKS1 (II-B/1) or by the accumulation of chitin in the fungal cell wall instead of β-glucan (II-B/2). Both resistance mechanisms against echinocandins caused attenuated virulence in C. parapsilosis and C. albicans in mice, Drosophilamelanogaster, and Galleria mellonella models (III-B/1-2). Polyenes form pores on the plasma membrane on fungal cells as these antifungals couple with ergosterol, which causes cell death (I-C). Resistance to polyenes can occur by LOF mutations in different genes playing role in the ergosterol biosynthetic pathway that leads to accumulation of alternative sterols, which has no toxic effect on the fungal cell membrane (II-C). These alterations in the ergosterol biosynthesis pathway cause attenuated virulence in C. tropicalis and C. albicans, regularly (III-C). Figures were created using images of BioRender and our own graphical elements.