Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence
Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is suspected to be one of the anti-oxidant enzymes and virulence determinants active in some pathogenic micro-organisms. To elucidate the role of Cu/ZnSOD in the major human fungal pathogen Candida albicans, its gene, designated SOD1, was disrupted by the URA-blaster technique. The resulting sod1/sod1 mutant showed delayed hyphal growth on Spider medium but could still form hyphae on other solid media or in liquid media, particularly in response to serum. Moreover, the sod1/sod1 mutant was more sensitive to menadione, a redox-cycling agent, than the isogenic wild-type strain, although it still showed an adaptive oxidative stress response. Furthermore, the sod1/sod1 mutant cells exhibited slow growth in minimal medium when compared to the wild-type cells, but their growth was restored by the addition of lysine to the medium. Interestingly, C. albicans cells lacking Cu/ZnSOD showed increased susceptibility to macrophage attack and had attenuated virulence in mice. Thus, these results suggest that Cu/ZnSOD is required for the protection of C. albicans against oxidative stresses and for the full virulence of the organism to be expressed.
ColemanD. C,
BennettD. E,
SullivanD. J,
GallagherP. J,
HenmanM. C,
StanleyM. B.,
RussellR. J.
1993; Oral Candida in HIV infection and AIDS: new perspectives/new approaches. Crit Rev Microbiol 19:61–82
DiezB,
SchleissnerC,
MorenoM. A,
RodriguezM,
ColladosA.,
BarredoJ. L.
1998; The manganese superoxide dismutase from the penicillin producer Penicillium chrysogenum
. Curr Genet 33:387–394
HongZ,
LoVerdeP. T,
HammarskjöldM. L.,
RekoshD.
1992; Schistosoma mansoni : cloning of a complementary DNA encoding cytosolic Cu/Zn superoxide dismutase and high-yield expression of the enzymatically active gene product in Escherichia coli
. Exp Parasitol 75:308–322
IzawaS,
InoueY.,
KimuraA.
1995; Oxidative stress response in yeast: effect of glutathione on adaptation to hydrogen peroxide stress in Saccharomyces cerevisiae
. FEBS Lett 368:73–76
JamiesonD. J,
StephenD. W. S.,
TerriereE. C.
1996; Analysis of the adaptive oxidative stress response of Candida albicans
. FEMS Microbiol Lett 138:83–88
KitayamaM.,
TogasakiR. K.
1995; Purification and cDNA isolation of chloroplastic phosphoglycerate kinase from Chlamydomonas reinhardtii
. Plant Physiol 107:393–400
LeeK. L,
BuckleyH. R.,
CampbellC. C.
1975; An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans
. Sabouraudia 13:148–153
Okado-MatsumotoA.,
FridovichI.
2001; Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem 276:38388–38393
RhieG.-e,
HwangC.-S,
BradyM. J.7 other authors1999; Manganese-containing superoxide dismutase and its gene from Candida albicans
. Biochim Biophys Acta1426409–419
RochaC. R,
SchroppelK,
HarcusD,
MarcilA,
DignardD,
TaylorB. N,
ThomasD. Y,
WhitewayM.,
LebererE.
2001; Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans
. Mol Biol Cell 12:3631–3643
WagnerD. K,
Collins-LechC.,
SohnleP. G.
1986; Inhibition of neutrophil killing of Candida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines. Infect Immun 51:731–735
WilksK. E,
DunnK. L. R,
FarrantJ. L,
ReddinK. M,
GorringeA. R,
LangfordP. R.,
KrollJ. S.
1998; Periplasmic superoxide dismutase in meningococcal pathogenicity. Infect Immun 66:213–217
WysongD. R,
ChristinL,
SugarA. M,
RobbinsP. W.,
DiamondR. D.
1998; Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect Immun 66:1953–1961
Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence