1887

Abstract

The maintenance of cellular calcium homeostasis is associated with cellular signalling transduction and the functions of many membrane compartments, especially endoplasmic reticulum (ER) function. ER-localized proteins that serve to maintain ER and cellular calcium homeostasis in are still unclear. In this study, Spf1, the putative homologue of the ER-localized P-type calcium ATPase ScSpf1, was investigated for its roles in cellular calcium homeostasis, hyphal development and virulence. We constructed an Spf1 null mutant which showed decreased vegetative growth rate and hypersensitivity to EGTA, high-level calcium and antifungal drugs. Similar to treatments of ER stress agents, deletion of stimulated calcium influx in the presence of FK506, resulting in an increase in cellular calcium contents, and induced expression of the calcium-dependent response elements gene , which is essential for the cell calcium survival pathway. Moreover, the null mutant had defects in hyphal development and biofilm formation, and was severely attenuated in virulence. These findings provided phenotypic evidence supporting roles for Spf1 in the maintenance of cellular calcium homeostasis, ER stress responses, hyphal development, biofilm formation and virulence in .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.057232-0
2012-09-01
2024-12-12
Loading full text...

Full text loading...

/deliver/fulltext/micro/158/9/2272.html?itemId=/content/journal/micro/10.1099/mic.0.057232-0&mimeType=html&fmt=ahah

References

  1. Ando A., Suzuki C. ( 2005). Cooperative function of the CHD5-like protein Mdm39p with a P-type ATPase Spf1p in the maintenance of ER homeostasis in Saccharomyces cerevisiae . Mol Genet Genomics 273:497–506 [View Article][PubMed]
    [Google Scholar]
  2. Bates S., MacCallum D. M., Bertram G., Munro C. A., Hughes H. B., Buurman E. T., Brown A. J., Odds F. C., Gow N. A. ( 2005). Candida albicans Pmr1p, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required for glycosylation and virulence. J Biol Chem 280:23408–23415 [View Article][PubMed]
    [Google Scholar]
  3. Bennett R. J., Johnson A. D. ( 2006). The role of nutrient regulation and the Gpa2 protein in the mating pheromone response of C. albicans . Mol Microbiol 62:100–119 [View Article][PubMed]
    [Google Scholar]
  4. Berman J., Sudbery P. E. ( 2002). Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet 3:918–932 [View Article][PubMed]
    [Google Scholar]
  5. Bonilla M., Cunningham K. W. ( 2003). Mitogen-activated protein kinase stimulation of Ca2+ signaling is required for survival of endoplasmic reticulum stress in yeast. Mol Biol Cell 14:4296–4305 [View Article][PubMed]
    [Google Scholar]
  6. Bonilla M., Nastase K. K., Cunningham K. W. ( 2002). Essential role of calcineurin in response to endoplasmic reticulum stress. EMBO J 21:2343–2353 [View Article][PubMed]
    [Google Scholar]
  7. Brand A., Shanks S., Duncan V. M. S., Yang M., Mackenzie K., Gow N. A. R. ( 2007). Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism. Curr Biol 17:347–352 [View Article][PubMed]
    [Google Scholar]
  8. Cronin S. R., Rao R., Hampton R. Y. ( 2002). Cod1p/Spf1p is a P-type ATPase involved in ER function and Ca2+ homeostasis. J Cell Biol 157:1017–1028 [View Article][PubMed]
    [Google Scholar]
  9. Dean N. ( 1995). Yeast glycosylation mutants are sensitive to aminoglycosides. Proc Natl Acad Sci U S A 92:1287–1291 [View Article][PubMed]
    [Google Scholar]
  10. Donlan R. M., Costerton J. W. ( 2002). Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15:167–193 [View Article][PubMed]
    [Google Scholar]
  11. Douglas L. J. ( 2003). Candida biofilms and their role in infection. Trends Microbiol 11:30–36 [View Article][PubMed]
    [Google Scholar]
  12. Finkel J. S., Mitchell A. P. ( 2011). Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118 [View Article][PubMed]
    [Google Scholar]
  13. Guarente L. ( 1983). Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast. Methods Enzymol 101:181–191 [View Article][PubMed]
    [Google Scholar]
  14. Herrero A. B., Magnelli P., Mansour M. K., Levitz S. M., Bussey H., Abeijon C. ( 2004). KRE5 gene null mutant strains of Candida albicans are avirulent and have altered cell wall composition and hypha formation properties. Eukaryot Cell 3:1423–1432 [View Article][PubMed]
    [Google Scholar]
  15. Hoyer L. L. ( 2001). The ALS gene family of Candida albicans . Trends Microbiol 9:176–180 [View Article][PubMed]
    [Google Scholar]
  16. Karababa M., Valentino E., Pardini G., Coste A. T., Bille J., Sanglard D. ( 2006). CRZ1, a target of the calcineurin pathway in Candida albicans . Mol Microbiol 59:1429–1451 [View Article][PubMed]
    [Google Scholar]
  17. Klepser M. E. ( 2006). Candida resistance and its clinical relevance. Pharmacotherapy 26:68S–75S [View Article][PubMed]
    [Google Scholar]
  18. LaFayette S. L., Collins C., Zaas A. K., Schell W. A., Betancourt-Quiroz M., Gunatilaka A. A., Perfect J. R., Cowen L. E. ( 2010). PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog 6:e1001069 [View Article][PubMed]
    [Google Scholar]
  19. Lapinskas P. J., Cunningham K. W., Liu X. F., Fink G. R., Culotta V. C. ( 1995). Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase. Mol Cell Biol 15:1382–1388[PubMed]
    [Google Scholar]
  20. Lesage G., Bussey H. ( 2006). Cell wall assembly in Saccharomyces cerevisiae . Microbiol Mol Biol Rev 70:317–343 [View Article][PubMed]
    [Google Scholar]
  21. Li F., Palecek S. P. ( 2008). Distinct domains of the Candida albicans adhesin Eap1p mediate cell–cell and cell–substrate interactions. Microbiology 154:1193–1203 [View Article][PubMed]
    [Google Scholar]
  22. Li F., Svarovsky M. J., Karlsson A. J., Wagner J. P., Marchillo K., Oshel P., Andes D., Palecek S. P. ( 2007). Eap1p, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo . Eukaryot Cell 6:931–939 [View Article][PubMed]
    [Google Scholar]
  23. Losev E., Papanikou E., Rossanese O. W., Glick B. S. ( 2008). Cdc1p is an endoplasmic reticulum-localized putative lipid phosphatase that affects Golgi inheritance and actin polarization by activating Ca2+ signaling. Mol Cell Biol 28:3336–3343 [View Article][PubMed]
    [Google Scholar]
  24. Marchi V., Sorin A., Wei Y., Rao R. ( 1999). Induction of vacuolar Ca2+-ATPase and H+/Ca2+ exchange activity in yeast mutants lacking Pmr1, the Golgi Ca2+-ATPase. FEBS Lett 454:181–186 [View Article][PubMed]
    [Google Scholar]
  25. Martin D. C., Kim H., Mackin N. A., Maldonado-Báez L., Evangelista C. C. Jr, Beaudry V. G., Dudgeon D. D., Naiman D. Q., Erdman S. E., Cunningham K. W. ( 2011). New regulators of a high affinity Ca2+ influx system revealed through a genome-wide screen in yeast. J Biol Chem 286:10744–10754 [View Article][PubMed]
    [Google Scholar]
  26. Nobbs A. H., Vickerman M. M., Jenkinson H. F. ( 2010). Heterologous expression of Candida albicans cell wall-associated adhesins in Saccharomyces cerevisiae reveals differential specificities in adherence and biofilm formation and in binding oral Streptococcus gordonii . Eukaryot Cell 9:1622–1634 [View Article][PubMed]
    [Google Scholar]
  27. Odds F. C., Kerridge D. ( 1985). Morphogenesis in Candida albicans . Crit Rev Microbiol 12:45–93 [View Article][PubMed]
    [Google Scholar]
  28. Onyewu C., Wormley F. L. Jr, Perfect J. R., Heitman J. ( 2004). The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans . Infect Immun 72:7330–7333 [View Article][PubMed]
    [Google Scholar]
  29. Palmgren M. G., Axelsen K. B. ( 1998). Evolution of P-type ATPases. Biochim Biophys Acta 1365:37–45 [View Article][PubMed]
    [Google Scholar]
  30. Pfaller M. A., Diekema D. J. ( 2007). Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163 [View Article][PubMed]
    [Google Scholar]
  31. Sanglard D., Ischer F., Marchetti O., Entenza J., Bille J. ( 2003). Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Mol Microbiol 48:959–976 [View Article][PubMed]
    [Google Scholar]
  32. Scarborough G. A. ( 1999). Structure and function of the P-type ATPases. Curr Opin Cell Biol 11:517–522 [View Article][PubMed]
    [Google Scholar]
  33. Scrimale T., Didone L., de Mesy Bentley K. L., Krysan D. J. ( 2009). The unfolded protein response is induced by the cell wall integrity mitogen-activated protein kinase signaling cascade and is required for cell wall integrity in Saccharomyces cerevisiae . Mol Biol Cell 20:164–175 [View Article][PubMed]
    [Google Scholar]
  34. Sheppard D. C., Yeaman M. R., Welch W. H., Phan Q. T., Fu Y., Ibrahim A. S., Filler S. G., Zhang M., Waring A. J., Edwards J. E. Jr ( 2004). Functional and structural diversity in the Als protein family of Candida albicans . J Biol Chem 279:30480–30489 [View Article][PubMed]
    [Google Scholar]
  35. Strayle J., Pozzan T., Rudolph H. K. ( 1999). Steady-state free Ca2+ in the yeast endoplasmic reticulum reaches only 10μM and is mainly controlled by the secretory pathway pump pmr1 . EMBO J 18:4733–4743 [View Article][PubMed]
    [Google Scholar]
  36. Sudbery P., Gow N., Berman J. ( 2004). The distinct morphogenic states of Candida albicans . Trends Microbiol 12:317–324 [View Article][PubMed]
    [Google Scholar]
  37. Umeyama T., Kaneko A., Watanabe H., Hirai A., Uehara Y., Niimi M., Azuma M. ( 2006). Deletion of the CaBIG1 gene reduces β-1,6-glucan synthesis, filamentation, adhesion, and virulence in Candida albicans . Infect Immun 74:2373–2381 [View Article][PubMed]
    [Google Scholar]
  38. Uppuluri P., Pierce C. G., Thomas D. P., Bubeck S. S., Saville S. P., Lopez-Ribot J. L. ( 2010). The transcriptional regulator Nrg1p controls Candida albicans biofilm formation and dispersion. Eukaryot Cell 9:1531–1537 [View Article][PubMed]
    [Google Scholar]
  39. Viladevall L., Serrano R., Ruiz A., Domenech G., Giraldo J., Barceló A., Ariño J. ( 2004). Characterization of the calcium-mediated response to alkaline stress in Saccharomyces cerevisiae . J Biol Chem 279:43614–43624 [View Article][PubMed]
    [Google Scholar]
  40. Yang M., Brand A., Srikantha T., Daniels K. J., Soll D. R., Gow N. A. ( 2011). Fig1 facilitates calcium influx and localizes to membranes destined to undergo fusion during mating in Candida albicans . Eukaryot Cell 10:435–444 [View Article][PubMed]
    [Google Scholar]
/content/journal/micro/10.1099/mic.0.057232-0
Loading
/content/journal/micro/10.1099/mic.0.057232-0
Loading

Data & Media loading...

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