Table 1.

Iron acquisition functions in Saccharomyces cerevisiae and selected fungal pathogens of humans

Type of transport system	Species	Protein	Functions	Virulence of mutants	Ref.
Reductive iron uptake
Ferric reductases
	S. cerevisiae	Fre1	Ferric iron reduction at the cell surface	NAa	17
	S. cerevisiae	Fre2	Ferric iron reduction at the cell surface	NA	17
	C. albicans	Fre7	Ferric iron reduction at the cell surface	NDb	21, 22 and 25
	C. albicans	Fre10	Ferric iron reduction at the cell surface	ND	21, 22 and 25
	C. albicans	Cfl1	Ferric iron reduction at the cell surface	Attenuation in a mouse model of systemic candidiasis	27
	C. neoformans	Fre2	Ferric iron reduction at the cell surface	Attenuation in a mouse model of cryptococcosis	29
	A. fumigatus	FreB	Ferric iron reduction at the cell surface	ND	41
Multicopper ferroxidase
	S. cerevisiae	Fet3	Multicopper oxidase. Ferrous iron oxidation and high-affinity iron uptake, coupled with Ftr1	NA	17
	C. albicans	Fet3	Putative multicopper oxidase	ND	32, 38 and 39
		Fet31	Ferrous iron oxidation and high-affinity iron uptake	Not required	32 and 38
		Fet33	Putative multicopper oxidase	Not required	39
		Fet34	Ferrous iron oxidation and high-affinity iron uptake, coupled with Ftr1	Attenuation in a mouse model of systemic candidiasis	38 and 39
		Fet99	Putative multicopper oxidase	ND	32 and 38
	C. glabrata	Fet3	Ferrous iron oxidation and high-affinity iron uptake	Reduced kidney colonization	37
	C. neoformans	Cfo1	Ferrous iron oxidation and high-affinity iron uptake	Attenuation in a mouse model of cryptococcosis	44
	C. neoformans	Cfo2	Putative multicopper oxidase	Not required	44
	A. fumigatus	fetC	Ferrous iron oxidation and high-affinity iron uptake	ND	36
	T. marneffei	fetC	Ferrous iron oxidation and high-affinity iron uptake	ND	49
Iron permease
	S. cerevisiae	Ftr1	High-affinity iron uptake, coupled with Fet3	NA	17
	C. albicans	Ftr1	High-affinity iron uptake, coupled with Fet3	Avirulent in a mouse model of systemic candidiasis	23
	C. albicans	Ftr2	Putative iron permease	Not required	23
	C. glabrata	Ftr1	High-affinity iron permease	Reduced kidney colonization	37 and 46
	C. neoformans	Cft1	High-affinity iron permease	Attenuation in a mouse model of cryptococcosis	35
	C. neoformans	Cft2	Putative iron permease	Not required	35
	C. neoformans	Cft3	Putative iron permease	Not required	43
	A. fumigatus	FtrA	High-affinity iron permease	Not required	36
	T. marneffei	Ftr1	High-affinity iron permease	No growth defect in macrophages	49
	R. oryzae	Ftr1	High-affinity iron permease	Reduced virulence in a mouse model of mucormycosis	63 and 64
Siderophore transportc
	S. cerevisiae	Arn1	Ferrichrome and ferrichrome A transport	NA	17, 24 and 53
		Arn2/Taf1	Triacetylfusarinine C transport	NA	17, 24 and 53
		Arn3/Sit1	Ferrichrome and ferrichrome A transport	NA	17, 24 and 53
		Arn4/Enb1	Enterobactin transport	NA	17, 24 and 53
	C. albicans	Arn1/Sit1	Ferrichrome-type xenosiderophore transport	Required for epithelial invasion	58–60
	C. glabrata	Sit1	Ferrichrome transport	Reduced survival within macrophages	37 and 61
	C. neoformans	Sit1	Ferrioxamine transport	Not required	62
	A. fumigatus	Sit1	Ferrichrome and ferrioxamine B transport	Not required	67
		Sit2	Ferrichrome transport	Not required	67
		MirB	Triacetylfusarinine C transport	ND	69
	H. capsulatum	Mfs1	Putative siderophore transporter	ND	70
		Abc1	Putative siderophore transporter	ND	70
	R. oryzae	Fob1, Fob2	Ferrioxamine binding at the cell surface	Required for virulence in a mouse model of mucormycosis	63
Heme assimilation
CFEM proteins
	C. albicans	Rbt5	Heme uptake, putative GPI-anchored hemoglobin receptor	Required for biofilm formation, not required for virulence	75 and 78
	C. albicans	Rbt51	Heme uptake	ND	75
	C. albicans	Pga7	Hemoglobin and heme utilization	Attenuation in a mouse model of systemic candidiasis	80
	C. glabrata	Ccw14	Unknown	Reduced survival in the liver and the spleen in a mouse model of systemic candidiasis	37
	P. lutzii	Rbt5	Putative hemoglobin receptor	Reduced survival in the spleen	84 and 85
ESCRT complex
	C. neoformans	Vps23	ESCRT-I complex, heme uptake	Avirulent in a mouse model of cryptococcosis	88
	C. neoformans	Vps22	ESCRT-II complex, heme uptake	Avirulent in a mouse model of cryptococcosis	89
	C. neoformans	Snf7	ESCRT-III complex, heme uptake	Avirulent in a mouse model of cryptococcosis	89
	C. neoformans	Vps20	ESCRT-III complex, heme uptake	ND	89
Hemophore
	C. albicans	Csa2	Putative hemophore	ND	77
	C. neoformans	Cig1	Putative hemophore	Not required, a cig1 and cfo1 double mutant shows attenuated virulence in a mouse model of cryptococcosis	90
Haemolysin
	C. glabrata	Mam3	Putative haemolysin	Reduced fungal burden in the kidney, liver and brain	37

^aNA: not applicable.

^bND: data not available

^cMutants defective in siderophore biosynthesis are attenuated in mouse models of virulence for A. fumigatus and H. capsulatum.^15,16,69