Microbiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Microbiology 148 (2002), 1061-1072
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
Right arrow Citation Map
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rustad, T. R.
Right arrow Articles by White, T. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rustad, T. R.
Right arrow Articles by White, T. C.
Agricola
Right arrow Articles by Rustad, T. R.
Right arrow Articles by White, T. C.
Microbiology (2002), 148, 1061-1072.
© 2002 Society for General Microbiology

Research Paper

Homozygosity at the Candida albicans MTL locus associated with azole resistance

Tige R. Rustad1,2, David A. Stevens3,4, Michael A. Pfaller5 and Theodore C. White1,2

Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA1
Seattle Biomedical Research Institute, 4 Nickerson St Suite 200, Seattle, WA 98109-1651, USA2
Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, San Jose, CA 95128, USA3
Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA 52242, USA4
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA5

Author for correspondence: Theodore C. White. Tel: +1 206 284 8846 ext. 344. Fax: +1 206 284 0313. e-mail: tedwhite{at}u.washington.edu

Antifungal drug resistance in the pathogenic fungus Candida albicans is a serious threat to the growing population of immunocompromised patients. This study describes a significant correlation between loss of heterozygosity at the C. albicans mating-type-like (MTL) locus and resistance to azole antifungals. A pool of 96 clinical isolates consisting of 50 azole-resistant or susceptible dose-dependent isolates and 46 azole-susceptible isolates was screened by PCR for the presence of MTLa1 and MTL{alpha}1. These genes were used as markers for the MTLa and MTL{alpha} loci. Both loci were present in 84 of the isolates. Six isolates failed to amplify MTLa1 and six failed to amplify MTL{alpha}1. Further PCR analysis demonstrated that loss of the MTLa1 and MTL{alpha}1 genes corresponded to loss of all of the loci-specific genes, resulting in homozygosity at the MTL locus. Southern analysis and single nucleotide polymorphism (SNP) analysis were used to determine that this loss of heterogeneity was due to replacement of one of the MTL loci with a duplicate of the other locus resulting in two homozygous copies of the MTL locus. Of the 12 homozygous isolates, one isolate was sensitive to azole drugs. Statistical analysis of the data demonstrates a strong correlation between homozygosity at the MTL locus and azole resistance (P<0·003). In a set of serial isolates, an increase in azole resistance correlated with the loss of heterozygosity at the MTL locus, lending further strength to the correlation. Gene disruptions of the MTL loci were found to have no effect on azole susceptibility.

Keywords: pathogenic fungi, mating locus, drug resistance

Abbreviations: CHEF, contour-clamped homogeneous electric field; chr, chromosome; EtBr, ethidium bromide; SNP, single nucleotide polymorphism




This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
A. R. Holmes, Y.-H. Lin, K. Niimi, E. Lamping, M. Keniya, M. Niimi, K. Tanabe, B. C. Monk, and R. D. Cannon
ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in Fluconazole-Resistant Candida albicans Clinical Isolates
Antimicrob. Agents Chemother., November 1, 2008; 52(11): 3851 - 3862.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
T. S. Richards, B. G. Oliver, and T. C. White
Micafungin activity against Candida albicans with diverse azole resistance phenotypes
J. Antimicrob. Chemother., August 1, 2008; 62(2): 349 - 355.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
A. Coste, A. Selmecki, A. Forche, D. Diogo, M.-E. Bougnoux, C. d'Enfert, J. Berman, and D. Sanglard
Genotypic Evolution of Azole Resistance Mechanisms in Sequential Candida albicans Isolates
Eukaryot. Cell, October 1, 2007; 6(10): 1889 - 1904.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
C.-Y. Lin, Y.-C. Chen, H.-J. Lo, K.-W. Chen, and S.-Y. Li
Assessment of Candida glabrata Strain Relatedness by Pulsed-Field Gel Electrophoresis and Multilocus Sequence Typing
J. Clin. Microbiol., August 1, 2007; 45(8): 2452 - 2459.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
F. C. Odds, M.-E. Bougnoux, D. J. Shaw, J. M. Bain, A. D. Davidson, D. Diogo, M. D. Jacobsen, M. Lecomte, S.-Y. Li, A. Tavanti, et al.
Molecular Phylogenetics of Candida albicans
Eukaryot. Cell, June 1, 2007; 6(6): 1041 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
S. MacPherson, M. Larochelle, and B. Turcotte
A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins
Microbiol. Mol. Biol. Rev., September 1, 2006; 70(3): 583 - 604.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
M.-E. Bougnoux, D. Diogo, N. Francois, B. Sendid, S. Veirmeire, J. F. Colombel, C. Bouchier, H. Van Kruiningen, C. d'Enfert, and D. Poulain
Multilocus Sequence Typing Reveals Intrafamilial Transmission and Microevolutions of Candida albicans Isolates from the Human Digestive Tract.
J. Clin. Microbiol., May 1, 2006; 44(5): 1810 - 1820.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. Coste, V. Turner, F. Ischer, J. Morschhauser, A. Forche, A. Selmecki, J. Berman, J. Bille, and D. Sanglard
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, April 1, 2006; 172(4): 2139 - 2156.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
N. Chauhan, T. Ciudad, A. Rodriguez-Alejandre, G. Larriba, R. Calderone, and E. Andaluz
Virulence and Karyotype Analyses of rad52 Mutants of Candida albicans: Regeneration of a Truncated Chromosome of a Reintegrant Strain (rad52/RAD52) in the Host
Infect. Immun., December 1, 2005; 73(12): 8069 - 8078.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
A. Tavanti, A. D. Davidson, M. J. Fordyce, N. A. R. Gow, M. C. J. Maiden, and F. C. Odds
Population Structure and Properties of Candida albicans, as Determined by Multilocus Sequence Typing
J. Clin. Microbiol., November 1, 2005; 43(11): 5601 - 5613.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
A. T. Coste, M. Karababa, F. Ischer, J. Bille, and D. Sanglard
TAC1, Transcriptional Activator of CDR Genes, Is a New Transcription Factor Involved in the Regulation of Candida albicans ABC Transporters CDR1 and CDR2
Eukaryot. Cell, December 1, 2004; 3(6): 1639 - 1652.
[Abstract] [Full Text] [PDF]

Home page
 Eukaryot CellHome page
M. L. Pendrak, S. S. Yan, and D. D. Roberts
Hemoglobin Regulates Expression of an Activator of Mating-Type Locus {alpha} Genes in Candida albicans
Eukaryot. Cell, June 1, 2004; 3(3): 764 - 775.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
C. Pujol, S. A. Messer, M. Pfaller, and D. R. Soll
Drug Resistance Is Not Directly Affected by Mating Type Locus Zygosity in Candida albicans
Antimicrob. Agents Chemother., April 1, 2003; 47(4): 1207 - 1212.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL MICROBIOLOGY J GEN VIROL
J MED MICROBIOL ALL SGM JOURNALS
Copyright © 2002 Society for General Microbiology.