Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Feb;65(2):829–832. doi: 10.1128/iai.65.2.829-832.1997

Avirulence of Candida albicans FAS2 mutants in a mouse model of systemic candidiasis.

X J Zhao 1, G E McElhaney-Feser 1, M J Sheridan 1, S E Broedel Jr 1, R L Cihlar 1
PMCID: PMC176135  PMID: 9009352

Abstract

Disruption of both alleles of the Candida albicans FAS2 gene abolishes the ability of the organism to establish infection in a murine model of systemic candidiasis. Within 72 h all mice inoculated with 10(6) CFU of the parental C. albicans strain had died. In contrast, all animals inoculated with the mutant strain CFD2 survived for the course of the experiment (21 days). Animals infected with either mutant strain CFD1 or CFD3, in which only one FAS2 allele was disrupted, also succumbed to infection, but mortality was not observed until 4 days postinfection and survivors remained for up to 20 days postinfection. The results demonstrate that FAS2 is required for successful C. albicans infection.

Full Text

The Full Text of this article is available as a PDF (281.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bulawa C. E., Miller D. W., Henry L. K., Becker J. M. Attenuated virulence of chitin-deficient mutants of Candida albicans. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10570–10574. doi: 10.1073/pnas.92.23.10570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cole M. F., Bowen W. H., Zhao X. J., Cihlar R. L. Avirulence of Candida albicans auxotrophic mutants in a rat model of oropharyngeal candidiasis. FEMS Microbiol Lett. 1995 Feb 15;126(2):177–180. doi: 10.1111/j.1574-6968.1995.tb07413.x. [DOI] [PubMed] [Google Scholar]
  3. Debono M., Gordee R. S. Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol. 1994;48:471–497. doi: 10.1146/annurev.mi.48.100194.002351. [DOI] [PubMed] [Google Scholar]
  4. Fonzi W. A., Irwin M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. doi: 10.1093/genetics/134.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fromtling R. A. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988 Apr;1(2):187–217. doi: 10.1128/cmr.1.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ghannoum M. A., Spellberg B., Saporito-Irwin S. M., Fonzi W. A. Reduced virulence of Candida albicans PHR1 mutants. Infect Immun. 1995 Nov;63(11):4528–4530. doi: 10.1128/iai.63.11.4528-4530.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ghannoum M. A., Spellberg B., Saporito-Irwin S. M., Fonzi W. A. Reduced virulence of Candida albicans PHR1 mutants. Infect Immun. 1995 Nov;63(11):4528–4530. doi: 10.1128/iai.63.11.4528-4530.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gillum A. M., Tsay E. Y., Kirsch D. R. Isolation of the Candida albicans gene for orotidine-5'-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet. 1984;198(2):179–182. doi: 10.1007/BF00328721. [DOI] [PubMed] [Google Scholar]
  9. Hector R. F. Compounds active against cell walls of medically important fungi. Clin Microbiol Rev. 1993 Jan;6(1):1–21. doi: 10.1128/cmr.6.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kirsch D. R., Whitney R. R. Pathogenicity of Candida albicans auxotrophic mutants in experimental infections. Infect Immun. 1991 Sep;59(9):3297–3300. doi: 10.1128/iai.59.9.3297-3300.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuziora M. A., Chalmers J. H., Jr, Douglas M. G., Hitzeman R. A., Mattick J. S., Wakil S. J. Molecular cloning of fatty acid synthetase genes from Saccharomyces cerevisiae. J Biol Chem. 1983 Oct 10;258(19):11648–11653. [PubMed] [Google Scholar]
  12. Shepherd M. G. Pathogenicity of morphological and auxotrophic mutants of Candida albicans in experimental infections. Infect Immun. 1985 Nov;50(2):541–544. doi: 10.1128/iai.50.2.541-544.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Smith S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J. 1994 Dec;8(15):1248–1259. [PubMed] [Google Scholar]
  14. Southard S. B., Cihlar R. L. Analysis and expression of the Candida albicans FAS2 gene. Gene. 1995 Apr 14;156(1):133–138. doi: 10.1016/0378-1119(95)00033-3. [DOI] [PubMed] [Google Scholar]
  15. Stoops J. K., Awad E. S., Arslanian M. J., Gunsberg S., Wakil S. J., Oliver R. M. Studies on the yeast fatty acid synthetase. Subunit composition and structural organization of a large multifunctional enzyme complex. J Biol Chem. 1978 Jun 25;253(12):4464–4475. [PubMed] [Google Scholar]
  16. Wakil S. J., Stoops J. K., Joshi V. C. Fatty acid synthesis and its regulation. Annu Rev Biochem. 1983;52:537–579. doi: 10.1146/annurev.bi.52.070183.002541. [DOI] [PubMed] [Google Scholar]
  17. Witkowski A., Rangan V. S., Randhawa Z. I., Amy C. M., Smith S. Structural organization of the multifunctional animal fatty-acid synthase. Eur J Biochem. 1991 Jun 15;198(3):571–579. doi: 10.1111/j.1432-1033.1991.tb16052.x. [DOI] [PubMed] [Google Scholar]
  18. Zhao X. J., McElhaney-Feser G. E., Bowen W. H., Cole M. F., Broedel S. E., Jr, Cihlar R. L. Requirement for the Candida albicans FAS2 gene for infection in a rat model of oropharyngeal candidiasis. Microbiology. 1996 Sep;142(Pt 9):2509–2514. doi: 10.1099/00221287-142-9-2509. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES