This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alarco, A.-M.
Right arrow Articles by Raymond, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alarco, A.-M.
Right arrow Articles by Raymond, M.

 Previous Article  |  Next Article 

Journal of Bacteriology, February 1999, p. 700-708, Vol. 181, No. 3
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The bZip Transcription Factor Cap1p Is Involved in Multidrug Resistance and Oxidative Stress Response in Candida albicans

Anne-Marie Alarco and Martine Raymond*

Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada H2W 1R7

Received 18 August 1998/Accepted 28 October 1998

Candida albicans is an opportunistic pathogenic yeast which frequently develops resistance to the antifungal agent fluconazole (FCZ) in patients undergoing long-term therapy. FCZ-resistant strains often display a reduced intracellular FCZ accumulation which correlates with the overexpression of the ATP-binding cassette transporters CDR1 and CDR2 or the major facilitator (MF) MDR1. We have recently cloned a C. albicans gene, named CAP1, which codes for a bZip transcription factor of the AP-1 family homologous to the Yap1 protein involved in multidrug resistance and response to oxidative stress in Saccharomyces cerevisiae. CAP1 was found to confer FCZ resistance in S. cerevisiae by transcriptionally activating FLR1, a gene coding for an MF homologous to the C. albicans MDR1 gene product (A.-M. Alarco, I. Balan, D. Talibi, N. Mainville, and M. Raymond, J. Biol. Chem. 272:19304-19313, 1997). To study the role of CAP1 in C. albicans, we constructed a CAI4-derived mutant strain carrying a homozygous deletion of the CAP1 gene (CJD21). We found that deletion of CAP1 did not affect the susceptibility of CJD21 cells to FCZ, cerulenin, brefeldin A, and diamide but caused hypersensitivity to cadmium, 4-nitroquinoline N-oxide, 1,10-phenanthroline, and hydrogen peroxide, an effect which was reverted by reintroduction of the CAP1 gene in these cells. Introduction of a hyperactive truncated allele of CAP1 (CAP1-TR) in CJD21 resulted in resistance of the cells to all of the above compounds except hydrogen peroxide. The hyperresistant phenotype displayed by the CJD21 CAP1-TR transformants was found to correlate with the overexpression of a number of potential CAP1 transcriptional targets such as MDR1, CaYCF1, CaGLR1, and CaTRR1. Taken together, our results demonstrate that CAP1 is involved in multidrug resistance and oxidative stress response in C. albicans. Finally, disruption of CAP1 in strain FR2, selected in vitro for FCZ resistance and constitutively overexpressing MDR1, did not suppress but rather increased the levels of MDR1 expression, demonstrating that CAP1 acts as a negative transcriptional regulator of the MDR1 gene in FR2 and is not responsible for MDR1 overexpression in this strain.

* Corresponding author. Mailing address: Institut de Recherches Cliniques de Montréal, 110 Pine Ave., West, Montréal, Québec, Canada H2W 1R7. Phone: (514) 987-5770. Fax: (514) 987-5732. E-mail: raymonm{at}ircm.qc.ca.

Journal of Bacteriology, February 1999, p. 700-708, Vol. 181, No. 3
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Rodaki, A., Bohovych, I. M., Enjalbert, B., Young, T., Odds, F. C., Gow, N. A.R., Brown, A. J.P. (2009). Glucose Promotes Stress Resistance in the Fungal Pathogen Candida albicans. Mol. Biol. Cell 20: 4845-4855 [Abstract] [Full Text]  
  • Arana, D. M., Nombela, C., Pla, J. (2009). Fluconazole at subinhibitory concentrations induces the oxidative- and nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the resistance of Candida albicans to phagocytes. J Antimicrob Chemother 0: dkp407v1-dkp407 [Abstract] [Full Text]  
  • Jain, C., Yun, M., Politz, S. M., Rao, R. P. (2009). A Pathogenesis Assay Using Saccharomyces cerevisiae and Caenorhabditis elegans Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis. Eukaryot Cell 8: 1218-1227 [Abstract] [Full Text]  
  • Znaidi, S., Barker, K. S., Weber, S., Alarco, A.-M., Liu, T. T., Boucher, G., Rogers, P. D., Raymond, M. (2009). Identification of the Candida albicans Cap1p Regulon. Eukaryot Cell 8: 806-820 [Abstract] [Full Text]  
  • Sellam, A., Askew, C., Epp, E., Lavoie, H., Whiteway, M., Nantel, A. (2009). Genome-wide Mapping of the Coactivator Ada2p Yields Insight into the Functional Roles of SAGA/ADA Complex in Candida albicans. Mol. Biol. Cell 20: 2389-2400 [Abstract] [Full Text]  
  • Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., Tanabe, K., Niimi, M., Goffeau, A., Monk, B. C. (2009). Efflux-Mediated Antifungal Drug Resistance. Clin. Microbiol. Rev. 22: 291-321 [Abstract] [Full Text]  
  • Alonso-Monge, R., Carvaihlo, S., Nombela, C., Rial, E., Pla, J. (2009). The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans. Microbiology 155: 413-423 [Abstract] [Full Text]  
  • Ramsdale, M., Selway, L., Stead, D., Walker, J., Yin, Z., Nicholls, S. M., Crowe, J., Sheils, E. M., Brown, A. J.P. (2008). MNL1 Regulates Weak Acid-induced Stress Responses of the Fungal Pathogen Candida albicans. Mol. Biol. Cell 19: 4393-4403 [Abstract] [Full Text]  
  • Cuellar-Cruz, M., Briones-Martin-del-Campo, M., Canas-Villamar, I., Montalvo-Arredondo, J., Riego-Ruiz, L., Castano, I., De Las Penas, A. (2008). High Resistance to Oxidative Stress in the Fungal Pathogen Candida glabrata Is Mediated by a Single Catalase, Cta1p, and Is Controlled by the Transcription Factors Yap1p, Skn7p, Msn2p, and Msn4p. Eukaryot Cell 7: 814-825 [Abstract] [Full Text]  
  • Lessing, F., Kniemeyer, O., Wozniok, I., Loeffler, J., Kurzai, O., Haertl, A., Brakhage, A. A. (2007). The Aspergillus fumigatus Transcriptional Regulator AfYap1 Represents the Major Regulator for Defense against Reactive Oxygen Intermediates but Is Dispensable for Pathogenicity in an Intranasal Mouse Infection Model. Eukaryot Cell 6: 2290-2302 [Abstract] [Full Text]  
  • Gulshan, K., Moye-Rowley, W. S. (2007). Multidrug Resistance in Fungi. Eukaryot Cell 6: 1933-1942 [Full Text]  
  • Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Tanabe, K., Niimi, M., Monk, B. C. (2007). Candida albicans drug resistance another way to cope with stress. Microbiology 153: 3211-3217 [Abstract] [Full Text]  
  • Molina, L., Kahmann, R. (2007). An Ustilago maydis Gene Involved in H2O2 Detoxification Is Required for Virulence. Plant Cell 19: 2293-2309 [Abstract] [Full Text]  
  • Enjalbert, B., MacCallum, D. M., Odds, F. C., Brown, A. J. P. (2007). Niche-Specific Activation of the Oxidative Stress Response by the Pathogenic Fungus Candida albicans. Infect. Immun. 75: 2143-2151 [Abstract] [Full Text]  
  • Argimon, S., Wishart, J. A., Leng, R., Macaskill, S., Mavor, A., Alexandris, T., Nicholls, S., Knight, A. W., Enjalbert, B., Walmsley, R., Odds, F. C., Gow, N. A. R., Brown, A. J. P. (2007). Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans. Eukaryot Cell 6: 682-692 [Abstract] [Full Text]  
  • Rognon, B., Kozovska, Z., Coste, A. T., Pardini, G., Sanglard, D. (2006). Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance. Microbiology 152: 3701-3722 [Abstract] [Full Text]  
  • Riggle, P. J., Kumamoto, C. A. (2006). Transcriptional Regulation of MDR1, Encoding a Drug Efflux Determinant, in Fluconazole-Resistant Candida albicans Strains through an Mcm1p Binding Site. Eukaryot Cell 5: 1957-1968 [Abstract] [Full Text]  
  • Hiller, D., Stahl, S., Morschhauser, J. (2006). Multiple cis-Acting Sequences Mediate Upregulation of the MDR1 Efflux Pump in a Fluconazole-Resistant Clinical Candida albicans Isolate.. Antimicrob. Agents Chemother. 50: 2300-2308 [Abstract] [Full Text]  
  • Enjalbert, B., Smith, D. A., Cornell, M. J., Alam, I., Nicholls, S., Brown, A. J.P., Quinn, J. (2006). Role of the Hog1 Stress-activated Protein Kinase in the Global Transcriptional Response to Stress in the Fungal Pathogen Candida albicans. Mol. Biol. Cell 17: 1018-1032 [Abstract] [Full Text]  
  • Sohn, K., Roehm, M., Urban, C., Saunders, N., Rothenstein, D., Lottspeich, F., Schroppel, K., Brunner, H., Rupp, S. (2005). Identification and Characterization of Cor33p, a Novel Protein Implicated in Tolerance towards Oxidative Stress in Candida albicans. Eukaryot Cell 4: 2160-2169 [Abstract] [Full Text]  
  • Tournu, H., Tripathi, G., Bertram, G., Macaskill, S., Mavor, A., Walker, L., Odds, F. C., Gow, N. A. R., Brown, A. J. P. (2005). Global Role of the Protein Kinase Gcn2 in the Human Pathogen Candida albicans. Eukaryot Cell 4: 1687-1696 [Abstract] [Full Text]  
  • Harry, J. B., Oliver, B. G., Song, J. L., Silver, P. M., Little, J. T., Choiniere, J., White, T. C. (2005). Drug-Induced Regulation of the MDR1 Promoter in Candida albicans. Antimicrob. Agents Chemother. 49: 2785-2792 [Abstract] [Full Text]  
  • Zhao, R., Daniels, K. J., Lockhart, S. R., Yeater, K. M., Hoyer, L. L., Soll, D. R. (2005). Unique Aspects of Gene Expression during Candida albicans Mating and Possible G1 Dependency. Eukaryot Cell 4: 1175-1190 [Abstract] [Full Text]  
  • MacPherson, S., Akache, B., Weber, S., De Deken, X., Raymond, M., Turcotte, B. (2005). Candida albicans Zinc Cluster Protein Upc2p Confers Resistance to Antifungal Drugs and Is an Activator of Ergosterol Biosynthetic Genes. Antimicrob. Agents Chemother. 49: 1745-1752 [Abstract] [Full Text]  
  • Lev, S., Hadar, R., Amedeo, P., Baker, S. E., Yoder, O. C., Horwitz, B. A. (2005). Activation of an AP1-Like Transcription Factor of the Maize Pathogen Cochliobolus heterostrophus in Response to Oxidative Stress and Plant Signals. Eukaryot Cell 4: 443-454 [Abstract] [Full Text]  
  • Nicholls, S., Straffon, M., Enjalbert, B., Nantel, A., Macaskill, S., Whiteway, M., Brown, A. J. P. (2004). Msn2- and Msn4-Like Transcription Factors Play No Obvious Roles in the Stress Responses of the Fungal Pathogen Candida albicans. Eukaryot Cell 3: 1111-1123 [Abstract] [Full Text]  
  • Karababa, M., Coste, A. T., Rognon, B., Bille, J., Sanglard, D. (2004). Comparison of Gene Expression Profiles of Candida albicans Azole-Resistant Clinical Isolates and Laboratory Strains Exposed to Drugs Inducing Multidrug Transporters. Antimicrob. Agents Chemother. 48: 3064-3079 [Abstract] [Full Text]  
  • Prusty, R., Grisafi, P., Fink, G. R. (2004). The plant hormone indoleacetic acid induces invasive growth in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 101: 4153-4157 [Abstract] [Full Text]  
  • Veal, E. A., Ross, S. J., Malakasi, P., Peacock, E., Morgan, B. A. (2003). Ybp1 Is Required for the Hydrogen Peroxide-induced Oxidation of the Yap1 Transcription Factor. J. Biol. Chem. 278: 30896-30904 [Abstract] [Full Text]  
  • Moye-Rowley, W. S. (2003). Regulation of the Transcriptional Response to Oxidative Stress in Fungi: Similarities and Differences. Eukaryot Cell 2: 381-389 [Full Text]  
  • 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 Candidaalbicans. Eukaryot Cell 2: 351-361 [Abstract] [Full Text]  
  • Enjalbert, B., Nantel, A., Whiteway, M. (2003). Stress-induced Gene Expression in Candida albicans: Absence of a General Stress Response. Mol. Biol. Cell 14: 1460-1467 [Abstract] [Full Text]  
  • Cowen, L. E., Nantel, A., Whiteway, M. S., Thomas, D. Y., Tessier, D. C., Kohn, L. M., Anderson, J. B. (2002). Population genomics of drug resistance in Candida albicans. Proc. Natl. Acad. Sci. USA 99: 9284-9289 [Abstract] [Full Text]  
  • Wirsching, S., Michel, S., Köhler, G., Morschhäuser, J. (2000). Activation of the Multiple Drug Resistance Gene MDR1 in Fluconazole-Resistant, Clinical Candida albicans Strains Is Caused by Mutations in a trans-Regulatory Factor. J. Bacteriol. 182: 400-404 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»