1887

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Volume 151, Issue 9

contributes to hyphal formation and virulence after the initial stages of disseminated candidiasis Free

Abstract

is a common cause of mucosal and bloodstream infections. As a screening strategy to identify novel candidal virulence factors, sera recovered from HIV-infected patients with active oropharyngeal candidiasis (OPC) were previously used to probe a genomic expression library. was identified as a gene that encodes an immunogenic protein. In the present study, the presence of transcripts was verified within OPC pseudomembranes recovered from patients. Having confirmed that the gene is expressed during human candidiasis, gene disruption strains were created and this implicated in diverse processes, including hyphal formation on solid media and under embedded conditions, cell wall integrity and structure, and adherence to human epithelial cells . disruption, however, did not influence hyphal formation or virulence in a murine model of OPC. Rather, the gene was found to be necessary for normal morphogenesis and full virulence during murine intravenously disseminated candidiasis (DC). 's effects on hyphal formation and virulence during DC were not evident on the first day after intravenous inoculation, even though transcripts were detected within murine kidneys. After 4 days, however, an null mutant strain was associated with attenuated mortality, diminished tissue burdens, less extensive infections, impaired hyphal formation and decreased kidney damage. Taken together, these findings suggest that makes distinct temporal-spatial contributions to the pathogenesis of candidiasis, which appear to vary between different tissue sites as well as within a given tissue over time.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): DC, disseminated candidiasis , FCS, fetal calf serum , FOA, fluoroorotic acid , GMS, gomori methenamine silver , HIV, human immunodeficiency virus , MAP, mitogen-activated protein , OMP, orotidine 5′-monophosphate , OPC, oropharyngeal candidiasis , PI(4,5)P2, phosphatidylinositol (4,5) bisphosphate , PMN, polymorphonuclear cell , SAP, secreted aspartyl proteinase and UMP, uridine 5′-monophosphate
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2005-09-01
2024-04-19
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References

  1. Brown D. H. Jr, Giusani A. D., Chen X., Kumamoto C. A. 1999; Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol Microbiol 34:651–662 [CrossRef]
     [Google Scholar]
  2. Calderone R. A., Fonzi W. A. 2001; Virulence factors of Candida albicans . Trends Microbiol 9:327–335 [CrossRef]
     [Google Scholar]
  3. Carson F. L. 1996; Histotechnology - a self instructional text. Lab Med 17:87–90
     [Google Scholar]
  4. Cheng S., Clancy C. J., Checkley M. A., Handfield M., Hillman J. D., Progulske-Fox A., Lewin A. S., Fidel P. L., Nguyen M. H. 2003a; Identification of Candida albicans genes induced during thrush offers insight into pathogenesis. Mol Microbiol 48:1275–1288 [CrossRef]
     [Google Scholar]
  5. Cheng S., Nguyen M. H., Zhang Z., Jia H., Handfield M., Clancy C. J. 2003b; Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus. Infect Immun 71:6101–6103 [CrossRef]
     [Google Scholar]
  6. Churukian C. J., Schenk E. A. 1977; Rapid Grocott's methenamine-silver nitrate method for fungi and Pneumocystis carinii . Am J Clin Pathol 68:427–428
     [Google Scholar]
  7. De Bernardis F., Muhlschegel F. A., Cassone A., Fonzi W. A. 1998; The pH of the host niche controls gene expression in and virulence of Candida albicans . Infect Immun 66:3317–3325
     [Google Scholar]
  8. Diez-Orejas R., Molero G., Navarro-Garcia F., Pla J., Nombela C., Sanchez-Perez M. 1997; Reduced virulence of Candida albicans MKC1 mutants: a role for mitogen-activated protein kinase in pathogenesis. Infect Immun 65:833–837
     [Google Scholar]
  9. Doedt T., Krishnamurthy S., Bockmuhl D. P., Tebarth B., Stempel C., Russell C. L., Brown A. J., Ernst J. F. 2004; apses proteins regulate morphogenesis and metabolism in Candida albicans . Mol Biol Cell 15:3167–3180 [CrossRef]
     [Google Scholar]
  10. Edmond M. B., Wallace S. E., McClish D. K., Pfaller M. A., Jones R. N., Wenzel R. P. 1999; Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29:239–244 [CrossRef]
     [Google Scholar]
  11. Ernst J. F. 2000; Transcription factors in Candida albicans : environmental control of morphogenesis. Microbiology 146:1763–1774
     [Google Scholar]
  12. Fonzi W. A., Irwin M. Y. 1993; Isogenic strain construction and gene mapping in Candida albicans . Genetics 134:717–728
     [Google Scholar]
  13. Fradin C., Kretschmar M., Nichterlein T., Gaillardin C., d'Enfert C., Hube B. 2003; Stage-specific gene expression of Candida albicans in human blood. Mol Microbiol 47:1523–1543 [CrossRef]
     [Google Scholar]
  14. Fu Y., Ibrahim A. S., Sheppard D. C., Chen Y. C., French S. W., Cutler J. E., Filler S. G., Edwards J. E. Jr 2002; Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway. Mol Microbiol 44:61–72 [CrossRef]
     [Google Scholar]
  15. Ghannoum M. A., Spellberg B., Saporito-Irwin S. M., Fonzi W. A. 1995; Reduced virulence of Candida albicans PHR1 mutants. Infect Immun 63:4528–4530
     [Google Scholar]
  16. Gow N. A., Brown A. J., Odds F. C. 2002; Fungal morphogenesis and host invasion. Curr Opin Microbiol 5:366–371 [CrossRef]
     [Google Scholar]
  17. Greenspan D. 1994; Treatment of oropharyngeal candidiasis in HIV-positive patients. J Am Acad Dermatol 31:S51–S55 [CrossRef]
     [Google Scholar]
  18. Lay J., Henry L. K., Clifford J., Koltin Y., Bulawa C. E., Becker J. M. 1998; Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies. Infect Immun 66:5301–5306
     [Google Scholar]
  19. Kamai Y., Kubota M., Kamai Y., Hosokawa T., Fukuoka T., Filler S. G. 2001; New model of oropharyngeal candidiasis in mice. Antimicrob Agents Chemother 45:3195–3197 [CrossRef]
     [Google Scholar]
  20. Kamai Y., Kubota M., Kamai Y., Hosokawa T., Fukuoka T., Filler S. G. 2002; Contribution of Candida albicans ALS1 to the pathogenesis of experimental oropharyngeal candidiasis. Infect Immun 70:5256–5258 [CrossRef]
     [Google Scholar]
  21. Mahan M. J., Heithoff D. M., Sinsheimer R. L., Low D. A. 2000; Assessment of bacterial pathogenesis by analysis of gene expression in the host. Annu Rev Genet 34:139–164 [CrossRef]
     [Google Scholar]
  22. Morales-Johansson H., Jenoe P., Cooke F. T., Hall M. N. 2004; Negative regulation of phosphatidylinositol 4,5-bisphosphate levels by the INP51-associated proteins TAX4 and IRS4. J Biol Chem 279:39604–39610 [CrossRef]
     [Google Scholar]
  23. Muhlschlegel F. A., Fonzi W. A. 1997; PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression. Mol Cell Biol 17:5960–5967
     [Google Scholar]
  24. Myers K. K., Sypherd P. S., Fonzi W. A. 1995; Use of URA3 as a reporter of gene expression in C. albicans . Curr Genet 27:243–248 [CrossRef]
     [Google Scholar]
  25. Naglik J. R., Newport G., White T. C., Fernandes-Naglik L. L., Greenspan J. S., Greenspan D., Sweet S. P., Challacombe S. J., Agabian N. 1999; In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis. Infect Immun 67:2482–2490
     [Google Scholar]
  26. Naglik J. R., Rodgers C. A., Shirlaw P. J., Dobbie J. L., Fernandes-Naglik L. L., Greenspan D., Agabian N., Challacombe S. J. 2003; Differential expression of Candida albicans secreted aspartyl proteinase and phospholipase B genes in humans correlates with active oral and vaginal infections. J Infect Dis 188:469–479 [CrossRef]
     [Google Scholar]
  27. Navarro-Garcia F., Sanchez M., Pla J., Nombela C. 1995; Functional characterization of the MKC1 gene of Candida albicans , which encodes a mitogen-activated protein kinase homolog related to cell integrity. Mol Cell Biol 15:2197–2206
     [Google Scholar]
  28. Navarro-Garcia F., Alonso-Monge R., Rico H., Pla J., Sentandreu R., Nombela C. 1998; A role for the MAP kinase gene MKC1 in cell wall construction and morphological transitions on Candida albicans . Microbiology 144:411–424 [CrossRef]
     [Google Scholar]
  29. Nguyen M. H., Cheng S., Clancy C. J. 2004; Assessment of Candida albicans genes expressed during infections as a tool to understand pathogenesis. Med Mycol 42:293–304 [CrossRef]
     [Google Scholar]
  30. Richet H., Roux P., Des Champs C., Esnault Y., Andremont A. A. 2002; Candidemia in French hospitals: incidence rates and characteristics. Clin Microbiol Infect 8:405–412 [CrossRef]
     [Google Scholar]
  31. Ripeau J. S., Fiorillo M., Aumont F., Belhumeur P., de Repentigny L. 2002; Evidence for differential expression of Candida albicans virulence genes during oral infection in intact and human immunodeficiency virus type 1-transgenic mice. J Infect Dis 185:1094–1102 [CrossRef]
     [Google Scholar]
  32. Santolini E., Salcini A. E., Kay B. K., Yamabhai M., Di Fiore P. P. 1999; The EH network. Exp Cell Res 253:186–209 [CrossRef]
     [Google Scholar]
  33. Schaller M., Schafer W., Korting H. C., Hube B. 1998; Differential expression of secreted aspartyl proteinases in a model of human oral candidiasis and in patient samples from the oral cavity. Mol Microbiol 29:605–615 [CrossRef]
     [Google Scholar]
  34. Staab J. F., Bradway S. D., Fidel P. L., Sundstrom P. 1999; Adhesive and mammaliam transglutaminase substrate properties of Candida albicans Hwp1. Science 283:1535–1538 [CrossRef]
     [Google Scholar]
  35. Staib P., Kretschmar M., Nichterlein T., Hof H., Morschhauser J. 2000a; Differential activation of a Candida albicans gene family during infection. Proc Natl Acad Sci U S A 97:6102–6107 [CrossRef]
     [Google Scholar]
  36. Staib P., Kretschmar M., Nichterlein T., Kohler G., Morschhauser J. 2000b; Expression of virulence genes in Candida albicans . Adv Exp Med Biol 485:167–176
     [Google Scholar]
  37. Sudbery P., Gow N., Berman J. 2004; The distinct morphogenic states of Candida albicans . Trends Microbiol 12:317–324 [CrossRef]
     [Google Scholar]
  38. Sundstrom P., Balish E., Allen C. M. 2002; Essential role of the Candida albicans transglutaminase substrate hyphal wall protein 1 in lethal oroesophageal candidiasis in immunodeficient mice. J Infect Dis 185:521–530 [CrossRef]
     [Google Scholar]
  39. Warenda A. J., Kauffman S., Sherrill T. P., Becker J. M., Konopka J. B. 2003; Candida albicans septin mutants are defective for invasive growth and virulence. Infect Immun 71:4045–4051 [CrossRef]
     [Google Scholar]
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Candida albicans IRS4 contributes to hyphal formation and virulence after the initial stages of disseminated candidiasis
Microbiology 151, 2923 (2005); https://doi.org/10.1099/mic.0.27998-0
/content/journal/micro/10.1099/mic.0.27998-0
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