Table 1

List of genes involved in hypoxia adaptation in human-pathogenic fungi and their role in virulencea

GeneFunctionOrganismHypoxia null mutant phenotype (reference[s])Role in virulence (reference[s])
UPC2Transcription factor, zinc cluster familyCandida albicansSignificant growth attenuation (75, 116)Not reported
CZF1Transcription factor, zinc finger domainC. albicansRequired for filamentous response to hypoxia (16)Not reported
EFG1Transcription factor, APSES familyC. albicansHyperfilamentous response to hypoxia (105)Increased in vivo proliferation (66), virulent but kinetics of mortality altered (73)
EFH1Transcription factor, APSES familyC. albicansNoneIncreased intestinal tract persistence (126)
TYE7Transcription factorC. albicansModerate growth defect (2)Significant attenuationb (2)
ACE2Transcription factor, Swi5 familyC. albicansRequired for filamentous response to hypoxia (79)Significant attenuation (65)
RAS1Small GTPaseC. albicansRequired for filamentous response to hypoxia (116)Significant attenuation (69)
CDC35 (CYR1)Adenylate cyclaseC. albicansRequired for filamentous response to hypoxia (116)Significant attenuation (95)
SCH9AGC protein kinaseC. albicansRequired for filamentous response to hypoxia (113)Significant attenuation (72)
TCO1Histidine kinase part of two-component regulatory systemCryptococcus neoformansSignificant growth attenuation (21)Significant attenuation (21)
SRE1Transcription factor, SREBP family, bHLHc DNA bindingC. neoformansSignificant growth attenuation (19, 21)Significant attenuation (19, 21)
SCP1Sterol cleavage-activating protein, senses sterols and is involved in Sre1 signalingC. neoformansSignificant growth attenuation (19, 21)Significant attenuation (21)
STP1Protease involved in proteolytic cleavage of Sre1C. neoformansSignificant growth attenuation (8, 21)Significant attenuation (8, 21)
KAP123Nuclear transport, involved in SRE1 pathwayC. neoformansSignificant growth attenuation (20)No attenuation (20)
GSK3Glycogen synthase kinase, involved in Sre1 turnover/phosphorylationC. neoformansSignificant growth attenuation (20)Significant attenuation (20)
srbATranscription factor, SREBP family, bHLH DNA bindingAspergillus fumigatusSignificant growth attenuation (128)Significant attenuation (128)
ireAType 1 membrane protein, protein kinase domain and endoribonuclease domainA. fumigatusModerate growth attenuation (37)Significant attenuation (37)
cycACytochrome cA. fumigatusModerate growth attenuationSignificant attenuation
ADH1Alcohol dehydrogenaseFusarium oxysporumModerate growth attenuation (22)Moderate attenuation (22)
  • a Does not include the cobalt chloride-sensitive C. neoformans mutants isolated from a T-DNA insertion mutagenesis library that are also sensitive to hypoxic growth. A list of these genes can be found in Table 1 of the original publication (56).

  • b Significant attenuation in Galleria mellonella model. Single Tye7 mutant virulence not reported in mice, but a gal4/tye7 strain is highly attenuated in A/J mice (4).

  • c bHLH, basic helix-loop-helix.