1887

Abstract

, clinically the most important human fungal pathogen, rapidly develops resistance to antifungal drugs. The acquisition of resistance has been linked to various types of genome changes. As part of an ongoing study of this problem, we investigated mutation, genome stability and drug resistance acquisition in strains with deletions in the base excision repair (BER) genes , and , and in the nucleotide excision repair (NER) genes and . The BER mutants did not exhibit any change in their susceptibility to DNA-damaging agents, but the NER mutants were extremely sensitive to UV-induced DNA damage. We did not observe any significant change in mutation, genome stability and antifungal drug sensitivity in the mutant strains we tested. However, we detected a number of intriguing phenotypic differences between strains bearing deletions in equivalent and BER and NER genes, which may be related to differences in the life cycles of these two fungi.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2008/017616-0
2008-08-01
2020-07-08
Loading full text...

Full text loading...

/deliver/fulltext/micro/154/8/2446.html?itemId=/content/journal/micro/10.1099/mic.0.2008/017616-0&mimeType=html&fmt=ahah

References

  1. Alonso-Monge R., Navarro-Garcia F., Molero G., Diez-Orejas R., Gustin M., Pla J., Sanchez M., Nombela C.. 1999; Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol181:3058–3068
    [Google Scholar]
  2. Alonso-Monge R., Navarro-Garcia F., Roman E., Negredo A. I., Eisman B., Nombela C., Pla J.. 2003; The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans. Eukaryot Cell2:351–361
    [Google Scholar]
  3. Andaluz E., Ciudad T., Gomez-Raja J., Calderone R., Larriba G.. 2006; Rad52 depletion in Candida albicans triggers both the DNA-damage checkpoint and filamentation accompanied by but independent of expression of hypha-specific genes. Mol Microbiol59:1452–1472
    [Google Scholar]
  4. Brachmann C. B., Davies A., Cost G. J., Caputo E., Li J., Hieter P., Boeke J. D.. 1998; Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast14:115–132
    [Google Scholar]
  5. Ciudad T., Andaluz E., Steinberg-Neifach O., Lue N. F., Gow N. A., Calderone R. A., Larriba G.. 2004; Homologous recombination in Candida albicans: role of CaRad52p in DNA repair, integration of linear DNA fragments and telomere length. Mol Microbiol53:1177–1194
    [Google Scholar]
  6. Glick M., Siegel M. A.. 1999; Viral and fungal infections of the oral cavity in immunocompetent patients. Infect Dis Clin North Am13:817–831
    [Google Scholar]
  7. Habraken Y., Sung P., Prakash L., Prakash S.. 1993; Yeast excision repair gene RAD2 encodes a single-stranded DNA endonuclease. Nature366:365–368
    [Google Scholar]
  8. Howlett N. G., Schiestl R. H.. 2004; Nucleotide excision repair deficiency causes elevated levels of chromosome gain in Saccharomyces cerevisiae. DNA Repair (Amst)3:127–134
    [Google Scholar]
  9. Ivanov E. L., Haber J. E.. 1995; RAD1 and RAD10, but not other excision repair genes, are required for double-strand break-induced recombination in Saccharomyces cerevisiae. Mol Cell Biol15:2245–2251
    [Google Scholar]
  10. Janbon G., Sherman F., Rustchenko E.. 1998; Monosomy of a specific chromosome determines l-sorbose utilization: a novel regulatory mechanism in Candida albicans. Proc Natl Acad Sci U S A95:5150–5155
    [Google Scholar]
  11. Kirkpatrick D. T., Petes T. D.. 1997; Repair of DNA loops involves DNA mismatch and nucleotide excision repair proteins. Nature387:929–931
    [Google Scholar]
  12. Legrand M., Lephart P., Forche A., Mueller F. M., Walsh T., Magee P. T., Magee B. B.. 2004; Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic rearrangements and tetraploid formation. Mol Microbiol52:1451–1462
    [Google Scholar]
  13. Legrand M., Chan C. L., Jauert P. A., Kirkpatrick D. T.. 2007; Role of DNA mismatch repair and double-strand break repair in genome stability and antifungal drug resistance in Candida albicans. Eukaryot Cell6:2194–2205
    [Google Scholar]
  14. Leng P., Sudbery P. E., Brown A. J.. 2000; Rad6p represses yeast–hypha morphogenesis in the human fungal pathogen Candida albicans. Mol Microbiol35:1264–1275
    [Google Scholar]
  15. Magee P. T., Bowdin L., Staudinger J.. 1992; Comparison of molecular typing methods for Candida albicans. J Clin Microbiol30:2674–2679
    [Google Scholar]
  16. Memisoglu A., Samson L.. 2000; Base excision repair in yeast and mammals. Mutat Res451:39–51
    [Google Scholar]
  17. Meshulam T., Levitz S. M., Christin L., Diamond R. D.. 1995; A simplified new assay for assessment of fungal cell damage with the tetrazolium dye, (2,3)-bis-(2-methoxy-4-nitro-5-sulphenyl)-(2H)-tetrazolium-5-carboxanilide (XTT. J Infect Dis172:1153–1156
    [Google Scholar]
  18. Miller G. R., Sarachek A.. 1974; Absence of photoreactivating enzyme in Candida albicans, Candida stellatoidea, and Candida tropicalis. Infect Immun10:398–399
    [Google Scholar]
  19. Murray J. M., Tavassoli M., al-Harithy R., Sheldrick K. S., Lehmann A. R., Carr A. M., Watts F. Z.. 1994; Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage. Mol Cell Biol14:4878–4888
    [Google Scholar]
  20. Noble S. M., Johnson A. D.. 2005; Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell4:298–309
    [Google Scholar]
  21. Perepnikhatka V., Fischer F. J., Niimi M., Baker R. A., Cannon R. D., Wang Y. K., Sherman F., Rustchenko E.. 1999; Specific chromosome alterations in fluconazole-resistant mutants of Candida albicans. J Bacteriol181:4041–4049
    [Google Scholar]
  22. Pittet D., Wenzel R. P.. 1995; Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths. Arch Intern Med155:1177–1184
    [Google Scholar]
  23. Selmecki A., Forche A., Berman J.. 2006; Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science313:367–370
    [Google Scholar]
  24. Shen J., Guo W., Kohler J. R.. 2005; CaNAT1, a heterologous dominant selectable marker for transformation of Candida albicans and other pathogenic Candida species. Infect Immun73:1239–1242
    [Google Scholar]
  25. Sun X., Thrower D., Qiu J., Wu P., Zheng L., Zhou M., Bachant J., Wilson D. M. III, Shen B.. 2003; Complementary functions of the Saccharomyces cerevisiae Rad2 family nucleases in Okazaki fragment maturation, mutation avoidance, and chromosome stability. DNA Repair (Amst)2:925–940
    [Google Scholar]
  26. Suvarnapunya A. E., Lagasse H. A., Stein M. A.. 2003; The role of DNA base excision repair in the pathogenesis of Salmonella enterica serovar Typhimurium. Mol Microbiol48:549–559
    [Google Scholar]
  27. Tomkinson A. E., Bardwell A. J., Bardwell L., Tappe N. J., Friedberg E. C.. 1993; Yeast DNA repair and recombination proteins Rad1 and Rad10 constitute a single-stranded-DNA endonuclease. Nature362:860–862
    [Google Scholar]
  28. Torres-Ramos C. A., Johnson R. E., Prakash L., Prakash S.. 2000; Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast. Mol Cell Biol20:3522–3528
    [Google Scholar]
  29. Winzeler E. A., Shoemaker D. D., Astromoff A., Liang H., Anderson K., Andre B., Bangham R., Benito R., Boeke J. D.. other authors 1999; Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science285:901–906
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2008/017616-0
Loading
/content/journal/micro/10.1099/mic.0.2008/017616-0
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