Table 1.

Involvement of selected regulatory proteins in virulence

Regulatory factor	Mutant phenotypes (virulence factors)	Virulence in mice	Other phenotypes	Influence on gene expression	Reference(s)
Cir1	Capsule defect, poor growth at host temp, enhanced melanization	Avirulent	Increased sensitivity to high iron, FK506, calcium, SDS, and amphotericin B and reduced sensitivity to miconazole	Regulation of functions for iron acquisition, cell wall and membrane biosynthesis, and signaling pathways (cAMP, Ca, MAPK)a and regulation of transcription factors	66
Cuf1	Melanin defect	Attenuated	Growth defect upon copper or iron limitation	Regulation of genes involved in copper homeostasis	35, 62, 63, 86, 134
Gat1	Capsule defect, enhanced growth at high temp, enhanced melanization	Slight hypervirulence or wild-type virulence	Essential for growth on some nitrogen sources (e.g., uric acid, urea, creatinine)	Regulation of nitrogen metabolism	73, 84
Gat201	Reduced capsule size, increased melanization, enhanced phagocytosis	Avirulent	Reduced lung infectivity	Regulation (upon Gat201 overexpression) of carbohydrate-related functions, including sugar transporters, glycosyl hydrolyases, and glycosyl transferases, and regulation of transcription factors	29, 88
Gcn5	Reduced capsule size and defect in capsule attachment, delayed growth at host temp	Avirulent	Increased sensitivity to FK506 and oxidative stress	Regulation of functions for cell wall biosynthesis and oxidative stress as well as transcription factors, signaling components, ribosomal proteins, and mitochondrial proteins	106
Nrg1	Capsule defect	Attenuated	Cell aggregation, mating defect, increased susceptibility to elevated salt and sorbitol stress and SDS	Regulation of genes for carbohydrate metabolism, sugar and siderophore transport, and oxidation/oxidative stress	32
Rim101	Capsule defect	Hypervirulent	Growth defects at alkaline pH, high salt, low iron	Regulation of metal homeostasis, cell wall proteins, and capsule-related genes	107
Sre1 (serotype A)	Subtle capsule and melanin defects	Attenuated	Sensitive to hypoxia	Regulation of functions related to stress, carbohydrate uptake and metabolism, respiration, sterol and heme biosynthesis, and fatty acid metabolism	30
Sre1 (serotype D)	Increased laccase activity, but no defects in capsule or melanin	Avirulent	Sensitive to hypoxia, growth defect on low-iron medium	Regulation of sterol biosynthesis, iron and copper transport, stress	24
Tup1 (serotype A)	Enlarged capsule, reduced melanin	Attenuated	Reduced mating, poor growth on low-iron and low-copper media, increased sensitivity to SDS and fluconazole	Regulation of iron and copper genes and capsule-related genes	83
Vad1	Melanin defect	Avirulent	Reduced growth on glucose medium with caffeine, on glycerol or lactate as carbon source, and on media with high salt or sorbitol	Regulation of NotI transcriptional regulator, laccases, phosphoenolpyruvate carboxykinase, elongation factor Tuf1, and a mannoprotein	109

^aMAPK, mitogen-activated protein kinase.