Table 1. Open in new tab Antifungal...

Antifungal class

Mode of action

Resistance mechanisms

References

Azole

Inhibit lanosterol 14 α-demethylase (Erg11p) in during the synthesis of ergosterol leading to formation of defective cell membrane and accumulation of toxic sterol metabolites

Point mutations in the lanosterol 14 α-demethylase (ERG11) gene; substitutions of Y132F, K143R, and F126L
Upregulation of the ERG11 expression
Increased copy number of ERG11
Overexpression of CDR genes members of the ATP-binding cassette (ABC) family and MDR1 member of the major facilitator superfamily (MFS) transporters
Increased copy numbers of transcription factor that regulate expression of ABC and MFS family transporters

^14,29,244

Echinocandins

Inhibits 1,3-beta-glucan synthase leading to defective cell wall formation

Mutations in the FKS1 gene encoding 1,3-beta-glucan synthase
FKS1 gene substitutions S639F, S639P, S639Y, S652Y

^29,35,36

Polyene

Binds to the membrane ergosterol and forms multimeric pores in the plasma membrane

Single nucleotide polymorphisms (SNPs) in different genomic loci

³²

Nucleoside analogs

Competitive inhibition of purine and pyrimidine uptake
Incorporation into fungal RNA to inhibit DNA and RNA synthesis

Amino acid substitution F211I in the FUR1 gene

³⁶

Table 1.

Open in new tab

Antifungal resistance mechanisms of C. auris.

Antifungal class	Mode of action	Resistance mechanisms	References
Azole	Inhibit lanosterol 14 α-demethylase (Erg11p) in during the synthesis of ergosterol leading to formation of defective cell membrane and accumulation of toxic sterol metabolites	Point mutations in the lanosterol 14 α-demethylase (ERG11) gene; substitutions of Y132F, K143R, and F126L Upregulation of the ERG11 expression Increased copy number of ERG11 Overexpression of CDR genes members of the ATP-binding cassette (ABC) family and MDR1 member of the major facilitator superfamily (MFS) transporters Increased copy numbers of transcription factor that regulate expression of ABC and MFS family transporters	^14,29,244
Echinocandins	Inhibits 1,3-beta-glucan synthase leading to defective cell wall formation	Mutations in the FKS1 gene encoding 1,3-beta-glucan synthase FKS1 gene substitutions S639F, S639P, S639Y, S652Y	^29,35,36
Polyene	Binds to the membrane ergosterol and forms multimeric pores in the plasma membrane	Single nucleotide polymorphisms (SNPs) in different genomic loci	³²
Nucleoside analogs	Competitive inhibition of purine and pyrimidine uptake Incorporation into fungal RNA to inhibit DNA and RNA synthesis	Amino acid substitution F211I in the FUR1 gene	³⁶

Antifungal class	Mode of action	Resistance mechanisms	References
Azole	Inhibit lanosterol 14 α-demethylase (Erg11p) in during the synthesis of ergosterol leading to formation of defective cell membrane and accumulation of toxic sterol metabolites	Point mutations in the lanosterol 14 α-demethylase (ERG11) gene; substitutions of Y132F, K143R, and F126L Upregulation of the ERG11 expression Increased copy number of ERG11 Overexpression of CDR genes members of the ATP-binding cassette (ABC) family and MDR1 member of the major facilitator superfamily (MFS) transporters Increased copy numbers of transcription factor that regulate expression of ABC and MFS family transporters	^14,29,244
Echinocandins	Inhibits 1,3-beta-glucan synthase leading to defective cell wall formation	Mutations in the FKS1 gene encoding 1,3-beta-glucan synthase FKS1 gene substitutions S639F, S639P, S639Y, S652Y	^29,35,36
Polyene	Binds to the membrane ergosterol and forms multimeric pores in the plasma membrane	Single nucleotide polymorphisms (SNPs) in different genomic loci	³²
Nucleoside analogs	Competitive inhibition of purine and pyrimidine uptake Incorporation into fungal RNA to inhibit DNA and RNA synthesis	Amino acid substitution F211I in the FUR1 gene	³⁶

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