Skip Navigation



JAC Advance Access published online on April 21, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki112
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/6/905    most recent
dki112v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Pasrija, R.
Right arrow Articles by Prasad, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pasrija, R.
Right arrow Articles by Prasad, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org
Received January 10, 2005
Revised February 28, 2005
Accepted March 1, 2005

Original article

Squalene epoxidase encoded by ERG1 affects morphogenesis and drug susceptibilities of Candida albicans

Ritu Pasrija 1 {dagger}, Shankarling Krishnamurthy 2 {ddagger}, Tulika Prasad 1, Joachim F. Ernst 2, and Rajendra Prasad 1*

1 School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India;
2 Institut für Mikrobiologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany

* To whom correspondence should be addressed.
Rajendra Prasad, E-mail: rp47{at}mail.jnu.ac.in


  Abstract

Objectives: Functional characterization of the erg1 mutant of ergosterol biosynthesis of Candida albicans.

Methods: We disrupted the ERG1 gene of C. albicans, which encodes squalene epoxidase (EC 1.14.99.7). Since the disruption of both alleles of ERG1 was lethal, the second allele of a heterozygous disruptant was placed under the control of a regulable promoter, MET3p, which is repressed by methionine and cysteine.

Results: The reverse-phase HPLC analysis of sterol, extracted from the conditional mutant strain, showed a total lack of ergosterol and instead accumulation of squalene. This imbalance in sterol composition led to defects in growth and increased susceptibilities to drugs including fluconazole, ketoconazole, cycloheximide, nystatin, amphotericin B and terbinafine. Reduced drug efflux activity of the erg1 mutant was associated with poor surface localization of Cdr1p, suggesting that enhanced passive diffusion and reduced efflux mediated by the ABC (ATP binding cassette) transporter Cdr1p increases drug susceptibility. Additionally, conditional erg1 mutant strains were unable to form hyphae in various media.

Conclusions: Taken together, our results demonstrate that the absence of ergosterol, which is one of the constituents of membrane microdomains (rafts), has a direct effect on drug susceptibility and morphogenesis of C. albicans.

Keywords: regulable promoter; hyphae; drug resistance; Cdr1p; ergosterol; dimorphism.

{dagger}Both authors contributed equally to this work.

{dagger}Both authors contributed equally to this work.

{ddagger}Present address. Department of Biochemistry, RWJMS Research Building, UMDNJ, 683 Hoes Lane West, Piscataway, NJ 08854, USA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
Y. Song, S. A. Cheon, K. E. Lee, S.-Y. Lee, B.-K. Lee, D.-B. Oh, H. A. Kang, and J.-Y. Kim
Role of the RAM Network in Cell Polarity and Hyphal Morphogenesis in Candida albicans
Mol. Biol. Cell, December 1, 2008; 19(12): 5456 - 5477.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
T. Iwaki, H. Iefuji, Y. Hiraga, A. Hosomi, T. Morita, Y. Giga-Hama, and K. Takegawa
Multiple functions of ergosterol in the fission yeast Schizosaccharomyces pombe
Microbiology, March 1, 2008; 154(3): 830 - 841.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
R. Pasrija, S. L. Panwar, and R. Prasad
Multidrug Transporters CaCdr1p and CaMdr1p of Candida albicans Display Different Lipid Specificities: both Ergosterol and Sphingolipids Are Essential for Targeting of CaCdr1p to Membrane Rafts
Antimicrob. Agents Chemother., February 1, 2008; 52(2): 694 - 704.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
S. Biswas, P. Van Dijck, and A. Datta
Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans
Microbiol. Mol. Biol. Rev., June 1, 2007; 71(2): 348 - 376.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
R. Pasrija, D. Banerjee, and R. Prasad
Structure and Function Analysis of CaMdr1p, a Major Facilitator Superfamily Antifungal Efflux Transporter Protein of Candida albicans: Identification of Amino Acid Residues Critical for Drug/H+ Transport
Eukaryot. Cell, March 1, 2007; 6(3): 443 - 453.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
S. M. Mulhern, M. E. Logue, and G. Butler
Candida albicans Transcription Factor Ace2 Regulates Metabolism and Is Required for Filamentation in Hypoxic Conditions
Eukaryot. Cell, December 1, 2006; 5(12): 2001 - 2013.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
P. D. Khot, P. A. Suci, R. L. Miller, R. D. Nelson, and B. J. Tyler
A Small Subpopulation of Blastospores in Candida albicans Biofilms Exhibit Resistance to Amphotericin B Associated with Differential Regulation of Ergosterol and {beta}-1,6-Glucan Pathway Genes
Antimicrob. Agents Chemother., November 1, 2006; 50(11): 3708 - 3716.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
M. Liu, M. D. Healy, B. A. Dougherty, K. M. Esposito, T. C. Maurice, C. E. Mazzucco, R. E. Bruccoleri, D. B. Davison, M. Frosco, J. F. Barrett, et al.
Conserved fungal genes as potential targets for broad-spectrum antifungal drug discovery.
Eukaryot. Cell, April 1, 2006; 5(4): 638 - 649.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.