Fluconazole resistance in Candida species: a current perspective

Figures & data

Table 1 Summary of molecular mechanisms of fluconazole resistance in Candida spp.

Mechanism	Gene(s) involveda	Regulator(s) involveda	Species
Drug target overexpression	ERG11	UPC2	Candida albicans, Candida parapsilosis, Candida tropicalis
Drug target alteration	ERG11		C. albicans, C. parapsilosis, C. tropicalis, Candida auris
Bypass pathways	ERG3		C. albicans, C. tropicalis
Efflux pump overexpression
ABC transporters	CDR1, CDR2, SNQ2, ABC1	TAC1, PDR1	C. albicans, Candida glabrata, C. parapsilosis, Candida krusei
MFS transporters	MDR1, TPO3	MRR1	C. albicans, C. parapsilosis, C. tropicalis, C. glabrata
Aneuploidy/loss of heterozygosity	ERG11	UPC2, TAC1	C. albicans

Note:

a Genes and regulators that have been directly linked to the resistant phenotype in clinical isolates.

Abbreviations: ABC, ATP-binding cassette; MFS, major facilitator superfamily.

Table 2 ERG11 amino acid substitutions linked to fluconazole resistance in clinical isolates of Candida albicans

Amino acid substitution	Hot spot	Reference
A61V		^Citation38
A114S	I	^Citation39
F126L	I	^Citation40
Y132F, Y132H	I	^Citation38^–^Citation41,Citation43
K143E, K143R, K143Q	I	^Citation38,Citation39,Citation42,Citation43
F145L	I	^Citation43
Y257H		^Citation39
N435V	III	^Citation39
S405F	III	^Citation34,Citation38,Citation40,Citation43
D446E	III	^Citation43
G448E	III	^Citation39,Citation43
F449S, F449V	III	^Citation38,Citation40,Citation43
G450E	III	^Citation43
G464S	III	^Citation36,Citation38,Citation40,Citation43
R467K	III	^Citation37
I471T	III	^Citation41
D502E		^Citation39

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