Disruption of the human pathogenic yeast Candida albicans catalase gene decreases survival in mouse-model infection and elevates susceptibility to higher temperature and to detergents.
Catalase-deficient strains of the human pathogenic yeast Candida albicans were constructed using the URA-blaster method. The disruptant was viable and grew normally in an ordinary culture condition, but became extremely sensitive to treatment with hydrogen peroxide. No catalase activity was observed in a catalase (CCT)-gene-disrupted strain, 1F5-4-1, suggesting that there were no other catalase or catalase-like enzymes in this yeast. The disruptant was shown to be sensitive to higher temperature and to low concentrations of SDS, NP-40, or Triton X-100. After a wild-type CCT gene was reintroduced into the disruptant, catalase activity was restored and the strain became moderately sensitive to treatment with hydrogen peroxide. However, neither the temperature sensitivity nor the susceptibility to SDS observed in the disruptant was restored in the CCT-reintroduced strain. A model infection experiment using wild-type and dCCT strains showed that the disruptants disappeared more rapidly than the wild-type strain in mouse liver, lung, and spleen. These results suggest that the catalase plays a significant role in survival in the host immune system and thus leads this organism to establish infection in the host.
Nakagawa
Yoshiyuki
Y
Laboratory of Medical Mycology, Research Institute for Disease Mechanism and Control, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Kanbe
Toshio
T
Mizuguchi
Ikuyo
I
D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D002177:Candidiasis / Q000382:microbiology*; D002374:Catalase / Q000235:genetics / Q000502:physiology*; D003520:Cyclophosphamide / Q000633:toxicity; D003902:Detergents / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D005816:Genetic Complementation Test; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D017830:Octoxynol / Q000494:pharmacology; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013104:Spheroplasts / Q000201:enzymology; D013154:Spleen / Q000382:microbiology; D014170:Transformation, Genetic
D003902:Detergents; D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D017830:Octoxynol; C010615:Nonidet P-40; D006861:Hydrogen Peroxide; D002374:Catalase