This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
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 Marr, K. A.
Right arrow Articles by White, T. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marr, K. A.
Right arrow Articles by White, T. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 1998, p. 2584-2589, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Rapid, Transient Fluconazole Resistance in Candida albicans Is Associated with Increased mRNA Levels of CDR

Kieren A. Marr,1,2,* Christopher N. Lyons,3 Tiger Rustad,2 Raleigh A. Bowden,1,2,4 and Theodore C. White3,5

Departments of Medicine,1 Pediatrics,4 and Pathobiology,5 University of Washington, Fred Hutchinson Cancer Research Center,2 and Seattle Biomedical Research Institute,3 Seattle, Washington

Received 2 April 1998/Returned for modification 13 May 1998/Accepted 29 June 1998

Fluconazole-resistant Candida albicans, a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as a cause of candidiasis in patients receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses of a series of C. albicans isolates from an MT patient who developed disseminated candidiasis caused by an azole-resistant strain 2 weeks after initiation of fluconazole prophylaxis (K. A. Marr, T. C. White, J. A. H. vanBurik, and R. A. Bowden, Clin. Infect. Dis. 25:908-910, 1997). DNA sequence analysis of the gene (ERG11) for the azole target enzyme, lanosterol demethylase, revealed no difference between sensitive and resistant isolates. A sterol biosynthesis assay revealed no difference in sterol intermediates between the sensitive and resistant isolates. Northern blotting, performed to quantify mRNA levels of genes encoding enzymes in the ergosterol biosynthesis pathway (ERG7, ERG9, and ERG11) and genes encoding efflux pumps (MDR1, ABC1, YCF, and CDR), revealed that azole resistance in this series is associated with increased mRNA levels for members of the ATP binding cassette (ABC) transporter superfamily, CDR genes. Serial growth of resistant isolates in azole-free media resulted in an increased susceptibility to azole drugs and corresponding decreased mRNA levels for the CDR genes. These results suggest that C. albicans can become transiently resistant to azole drugs rapidly after exposure to fluconazole, in association with increased expression of ABC transporter efflux pumps.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. D3-100, Seattle, WA 98109. Phone: (206) 667-2995. Fax: (206) 667-4411. E-mail: kmarr{at}u.washington.edu.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2584-2589, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Sionov, E., Chang, Y. C., Garraffo, H. M., Kwon-Chung, K. J. (2009). Heteroresistance to Fluconazole in Cryptococcus neoformans Is Intrinsic and Associated with Virulence. Antimicrob. Agents Chemother. 53: 2804-2815 [Abstract] [Full Text]  
  • Xu, Y., Chen, L., Li, C. (2008). Susceptibility of clinical isolates of Candida species to fluconazole and detection of Candida albicans ERG11 mutations. J Antimicrob Chemother 61: 798-804 [Abstract] [Full Text]  
  • Oliver, B. G., Song, J. L., Choiniere, J. H., White, T. C. (2007). cis-Acting Elements within the Candida albicans ERG11 Promoter Mediate the Azole Response through Transcription Factor Upc2p. Eukaryot Cell 6: 2231-2239 [Abstract] [Full Text]  
  • Perumal, P., Mekala, S., Chaffin, W. L. (2007). Role for Cell Density in Antifungal Drug Resistance in Candida albicans Biofilms. Antimicrob. Agents Chemother. 51: 2454-2463 [Abstract] [Full Text]  
  • Selmecki, A., Forche, A., Berman, J. (2006). Aneuploidy and Isochromosome Formation in Drug-Resistant Candida albicans.. Science 313: 367-370 [Abstract] [Full Text]  
  • Andes, D., Forrest, A., Lepak, A., Nett, J., Marchillo, K., Lincoln, L. (2006). Impact of Antimicrobial Dosing Regimen on Evolution of Drug Resistance In Vivo: Fluconazole and Candida albicans.. Antimicrob. Agents Chemother. 50: 2374-2383 [Abstract] [Full Text]  
  • Yang, C.-R., Zhang, Y., Jacob, M. R., Khan, S. I., Zhang, Y.-J., Li, X.-C. (2006). Antifungal activity of C-27 steroidal saponins.. Antimicrob. Agents Chemother. 50: 1710-1714 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Sheehan, D. J. (2006). Interpretive Breakpoints for Fluconazole and Candida Revisited: a Blueprint for the Future of Antifungal Susceptibility Testing. Clin. Microbiol. Rev. 19: 435-447 [Abstract] [Full Text]  
  • Uko, S., Soghier, L. M., Vega, M., Marsh, J., Reinersman, G. T., Herring, L., Dave, V. A., Nafday, S., Brion, L. P. (2006). Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants. Pediatrics 117: 1243-1252 [Abstract] [Full Text]  
  • Coste, A., Turner, V., Ischer, F., Morschhauser, J., Forche, A., Selmecki, A., Berman, J., Bille, J., Sanglard, D. (2006). A Mutation in Tac1p, a Transcription Factor Regulating CDR1 and CDR2, Is Coupled With Loss of Heterozygosity at Chromosome 5 to Mediate Antifungal Resistance in Candida albicans. Genetics 172: 2139-2156 [Abstract] [Full Text]  
  • Borst, A., Raimer, M. T., Warnock, D. W., Morrison, C. J., Arthington-Skaggs, B. A. (2005). Rapid Acquisition of Stable Azole Resistance by Candida glabrata Isolates Obtained before the Clinical Introduction of Fluconazole. Antimicrob. Agents Chemother. 49: 783-787 [Abstract] [Full Text]  
  • Burn, A. K., Fothergill, A. W., Kirkpatrick, W. R., Coco, B. J., Patterson, T. F., McCarthy, D. I., Rinaldi, M. G., Redding, S. W. (2004). Comparison of Antifungal Susceptibilities to Fluconazole and Voriconazole of Oral Candida glabrata Isolates from Head and Neck Radiation Patients. J. Clin. Microbiol. 42: 5846-5848 [Abstract] [Full Text]  
  • Chau, A. S., Mendrick, C. A., Sabatelli, F. J., Loebenberg, D., McNicholas, P. M. (2004). Application of Real-Time Quantitative PCR to Molecular Analysis of Candida albicans Strains Exhibiting Reduced Susceptibility to Azoles. Antimicrob. Agents Chemother. 48: 2124-2131 [Abstract] [Full Text]  
  • Frade, J. P., Warnock, D. W., Arthington-Skaggs, B. A. (2004). Rapid Quantification of Drug Resistance Gene Expression in Candida albicans by Reverse Transcriptase LightCycler PCR and Fluorescent Probe Hybridization. J. Clin. Microbiol. 42: 2085-2093 [Abstract] [Full Text]  
  • Song, J. L., Harry, J. B., Eastman, R. T., Oliver, B. G., White, T. C. (2004). The Candida albicans Lanosterol 14-{alpha}-Demethylase (ERG11) Gene Promoter Is Maximally Induced after Prolonged Growth with Antifungal Drugs. Antimicrob. Agents Chemother. 48: 1136-1144 [Abstract] [Full Text]  
  • Balajee, S. A., Weaver, M., Imhof, A., Gribskov, J., Marr, K. A. (2004). Aspergillus fumigatus Variant with Decreased Susceptibility to Multiple Antifungals. Antimicrob. Agents Chemother. 48: 1197-1203 [Abstract] [Full Text]  
  • Lee, M.-K., Williams, L. E., Warnock, D. W., Arthington-Skaggs, B. A. (2004). Drug resistance genes and trailing growth in Candida albicans isolates. J Antimicrob Chemother 53: 217-224 [Abstract] [Full Text]  
  • Leber, R., Fuchsbichler, S., Klobucnikova, V., Schweighofer, N., Pitters, E., Wohlfarter, K., Lederer, M., Landl, K., Ruckenstuhl, C., Hapala, I., Turnowsky, F. (2003). Molecular Mechanism of Terbinafine Resistance in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 47: 3890-3900 [Abstract] [Full Text]  
  • Pinjon, E., Moran, G. P., Jackson, C. J., Kelly, S. L., Sanglard, D., Coleman, D. C., Sullivan, D. J. (2003). Molecular Mechanisms of Itraconazole Resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 47: 2424-2437 [Abstract] [Full Text]  
  • Lupetti, A., Paulusma-Annema, A., Welling, M. M., Dogterom-Ballering, H., Brouwer, C. P. J. M., Senesi, S., van Dissel, J. T., Nibbering, P. H. (2003). Synergistic Activity of the N-Terminal Peptide of Human Lactoferrin and Fluconazole against Candida Species. Antimicrob. Agents Chemother. 47: 262-267 [Abstract] [Full Text]  
  • Yamazumi, T., Pfaller, M. A., Messer, S. A., Houston, A. K., Boyken, L., Hollis, R. J., Furuta, I., Jones, R. N. (2003). Characterization of Heteroresistance to Fluconazole among Clinical Isolates of Cryptococcus neoformans. J. Clin. Microbiol. 41: 267-272 [Abstract] [Full Text]  
  • White, T. C., Holleman, S., Dy, F., Mirels, L. F., Stevens, D. A. (2002). Resistance Mechanisms in Clinical Isolates of Candida albicans. Antimicrob. Agents Chemother. 46: 1704-1713 [Abstract] [Full Text]  
  • Rustad, T. R., Stevens, D. A., Pfaller, M. A., White, T. C. (2002). Homozygosity at the Candida albicans MTL locus associated with azole resistance. Microbiology 148: 1061-1072 [Abstract] [Full Text]  
  • Perea, S., Lopez-Ribot, J. L., Kirkpatrick, W. R., McAtee, R. K., Santillan, R. A., Martinez, M., Calabrese, D., Sanglard, D., Patterson, T. F. (2001). Prevalence of Molecular Mechanisms of Resistance to Azole Antifungal Agents in Candida albicans Strains Displaying High-Level Fluconazole Resistance Isolated from Human Immunodeficiency Virus-Infected Patients. Antimicrob. Agents Chemother. 45: 2676-2684 [Abstract] [Full Text]  
  • Xu, J., Onyewu, C., Yoell, H. J., Ali, R. Y., Vilgalys, R. J., Mitchell, T. G. (2001). Dynamic and Heterogeneous Mutations to Fluconazole Resistance in Cryptococcus neoformans. Antimicrob. Agents Chemother. 45: 420-427 [Abstract] [Full Text]  
  • Marr, K. A., Lyons, C. N., Ha, K., Rustad, T. R., White, T. C. (2001). Inducible Azole Resistance Associated with a Heterogeneous Phenotype in Candida albicans. Antimicrob. Agents Chemother. 45: 52-59 [Abstract] [Full Text]  
  • Lyons, C. N., White, T. C. (2000). Transcriptional Analyses of Antifungal Drug Resistance in Candida albicans. Antimicrob. Agents Chemother. 44: 2296-2303 [Abstract] [Full Text]  
  • Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., Giacometti, A., Gavaudan, S., Scalise, G. (2000). Experimental Induction of Fluconazole Resistance in Candida tropicalis ATCC 750. Antimicrob. Agents Chemother. 44: 1578-1584 [Abstract] [Full Text]  
  • Marichal, P., Koymans, L., Willemsens, S., Bellens, D., Verhasselt, P., Luyten, W., Borgers, M., Ramaekers, F. C. S., Odds, F. C., Vanden Bossche, H. (1999). Contribution of mutations in the cytochrome P450 14{alpha}-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Microbiology 145: 2701-2713 [Abstract] [Full Text]  
  • Mondon, P., Petter, R., Amalfitano, G., Luzzati, R., Concia, E., Polacheck, I., Kwon-Chung, K. J. (1999). Heteroresistance to Fluconazole and Voriconazole in Cryptococcus neoformans. Antimicrob. Agents Chemother. 43: 1856-1861 [Abstract] [Full Text]  
  • Ha, K. C., White, T. C. (1999). Effects of Azole Antifungal Drugs on the Transition from Yeast Cells to Hyphae in Susceptible and Resistant Isolates of the Pathogenic Yeast Candida albicans. Antimicrob. Agents Chemother. 43: 763-768 [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»