1887

Abstract

Summary: The basis of cerulenin resistance of strains 4918-2 and 4918-10 has been investigated. Parasexual genetic analyses established that cerulenin resistance to concentrations of at least 5 μg ml is dominant in both strains. The results also showed that strain 4918-2 is heterozygous for resistance, while the change from resistance to sensitivity of strain 4918-10 is reversible. Experiments to define the mechanism(s) responsible for resistance focused on cerulenin uptake and fatty-acid synthase activity. Cerulenin uptake by strains 4918-2 and 4918-10 was 24% of that of the wild-type (strain 4918). Uptake was restored in UV-induced cerulenin-sensitive segregants of strains 4918-2 and 4918-10, and varied from 63% to 200% of parental values. Fatty-acid synthase from strains 4918-2 and 4918-10 was resistant to cerulenin as judged by differences in the inactivation of the enzyme by the agent. However, inactivation kinetics of fatty-acid synthase of cerulenin-sensitive segregants did not revert to the parental inactivation profile. Further investigation showed that nine out of ten segregants were resistant to cerulenin at concentrations between 1 and 4 μg ml while strain 4918 was sensitive to cerulenin at all concentrations tested. Thus, the results suggest that alteration of fatty-acid synthase and changes in permeability contribute to total cerulenin resistance of each strain.

Loading

Article metrics loading...

/content/journal/micro/10.1099/13500872-141-7-1553
1995-07-01
2021-10-25
Loading full text...

Full text loading...

/deliver/fulltext/micro/141/7/mic-141-7-1553.html?itemId=/content/journal/micro/10.1099/13500872-141-7-1553&mimeType=html&fmt=ahah

References

  1. Calderone R.A., Cihlar R.L., Lee D.D.S., Hoberg K., Scheld M. 1986; Yeast adhesion in the pathogenesis of endocarditis due to Candida albicans-, studies with adherence-negative mutants.. J Infect Dis 152:710–715
    [Google Scholar]
  2. Cihlar R.L., Hoberg K., Calderone R.A. 1984; Isolation of cerulenin-resistant mutants of Candida albicans. . In Microbiology-1984 pp. 148–149 Levine L., Schlesinger D. Edited by Washington, DC: American Society for Microbiology;
    [Google Scholar]
  3. Cutler 1.E. 1991; Putative virulence factors of Candida albicans.. Annu Rev Biochem 45:187–218
    [Google Scholar]
  4. De Bernardis F., Adriani D., Lorenzini R., Pontieu E., Carruba G., Cassone A. 1993; Filamentous growth and elevated vagino- pathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection.. Infect Immun 61:1500–1508
    [Google Scholar]
  5. Funabashi H., Kawaguchi A., Tomoda H., Ōmura S., Okuda S. 1989; Binding site of cerulenin in fatty acid synthase.. J Biochem 105:751–755
    [Google Scholar]
  6. Goshorn A.K., Scherer S. 1989; Genetic analysis of proto-trophic natural variants of Candida albicans.. Genetics 123:667–673
    [Google Scholar]
  7. Hoberg K.A., Cihlar R.L., Calderone R.A. 1986; Charac-terization of cerulenin-resistant mutants of Candida albicans.. Infect Immun 51:102–109
    [Google Scholar]
  8. Hostetter M.K. 1994; Adhesions and ligands involved in the interaction of Candida spp. with epithelial and endothelial surfaces.. Clin Microbiol Rev 7:29–42
    [Google Scholar]
  9. Inokoshi J., Tomoda H., Hashimoto H., Watanabe A., Takeshima H., Ōmura S. 1994; Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene.. Mol & Gen Genet 244:90–96
    [Google Scholar]
  10. Lehrer N., Segal E., Cihlar R.L., Calderon R.A. 1986; Pathogenesis of vaginal candidiasis: a mutant which has reduced ability to adhere in vitro.. J Med Vet Mycol 24:127–131
    [Google Scholar]
  11. Lynen F. 1969; Yeast fatty acid synthase.. Methods Ensymol 14:17–33
    [Google Scholar]
  12. Malavasic M.J., McElhaney-Feser G.E., Southard S.B., Cihlar R.L. 1991; Phenotypic variation of a virulent Candida albicans strain and two spontaneous, relatively avirulent mutant strain derivatives.. J Med Vet Mycol 29:145–155
    [Google Scholar]
  13. Manning M., Mitchell T.G. 1980; Strain variation and morphogenesis of yeast and mycelial-phase Candida albicans in low sulfate, synthetic medium.. J Bacteriol 142:714–719
    [Google Scholar]
  14. McElhaney-Feser G.E., Cihlar R.L. 1994; Purification and characterization of fatty acid synthase from Candida albicans, strain 4918, and two derived spontaneous cerulenin-resistant mutants.. J Med Vet Mycol 32:13–20
    [Google Scholar]
  15. Miller J.H. 1972 Experiments in Molecular Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  16. Odds F.C. 1988 Candida and Candidosis. London: Bailliere Tindall;
    [Google Scholar]
  17. Ollert M.W., Wadsworth E., Calderone R.A. 1990; Reduced expression of the functionally active complement receptor for iC3b on an avirulent mutant of Candida albicans.. Infect Immun 58:909–913
    [Google Scholar]
  18. Ōmura S. 1981; Cerulenin.. Methods Enaymol 72:520–532
    [Google Scholar]
  19. Ross I.K., De Bernardis F., Emerson G.W., Cassone A., Sullivan P.A. 1990; The secreted aspartate proteinase of Candida albicans-, physiology of secretion and virulence of a proteinase deficient mutant.. J Gen Microbiol 136:687–694
    [Google Scholar]
  20. Saxena A., Hammer C.F., Cihlar R.L. 1989; Analysis of mannans of two relatively avirulent strains of Candida albicans.. Infect Immun 57:413–419
    [Google Scholar]
  21. Saxena A., McElhaney-Feser G.E., Cihlar R.L. 1990; Mannan composition of the hyphal form of two relatively avirulent mutants of Candida albicans.. Infect Immun 58:2061–2066
    [Google Scholar]
  22. Slutsky B., Buffo J., Soll D.R. 1985; High-frequency switching of colony morphology in Candida albicans.. Science 230:666–669
    [Google Scholar]
  23. Soll D.R. 1992; High frequency switching in Candida albicans.. Clin Microbiol Ren 5:183–203
    [Google Scholar]
  24. Southard S.B., Cihlar R.L. 1995; Analysis and expression of the Candida albicans FAS2 gene.. Gene 156:133–138
    [Google Scholar]
  25. Whelan W.L., Magee P.T. 1981; Natural heterozygosity in Candida albicans.. J Bacteriol 145:896–903
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/13500872-141-7-1553
Loading
/content/journal/micro/10.1099/13500872-141-7-1553
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error