Inducible azole resistance associated with a heterogeneous phenotype in Candida albicans

被引:84
作者
Marr, KA
Lyons, CN
Ha, K
Rustad, TR
White, TC
机构
[1] Fred Hutchinson Canc Res Ctr, Program Infect Dis, Seattle, WA 98109 USA
[2] Univ Washington, Dept Med, Seattle, WA USA
[3] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA
[4] Seattle Biomed Res Inst, Seattle, WA 98109 USA
关键词
D O I
10.1128/AAC.45.1.52-59.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The development of azole resistance in Candida albicans is most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently, the rapid development of resistance was noted in other immunosuppressed patients who developed disseminated candidiasis despite fluconazole prophylaxis. One of these series of C. albicans isolates became resistant, with an associated increase in mRNA specific for a CDR ATP-binding cassette transporter efflux pump (K. A. Marr, C. N. Lyons, T. R. Rustad, R. A. Bowden, and T. C. White, Antimicrob. Agents Chemother. 42:2584-2589, 1998). Here we study this series of C. albicans isolates further and examine the mechanism of azole resistance in a second series of C. albicans isolates that caused disseminated infection in a recipient of bone marrow transplantation. The susceptible isolates in both series become resistant to fluconazole after serial growth in the presence of drug, while the resistant isolates in both series become susceptible after serial transfer in the absence of drug. Population analysis of the inducible, transiently resistant isolates reveals a heterogeneous population of fluconazole-susceptible and -resistant cells. We conclude that the rapid development of azole resistance occurs by a mechanism that involves selection of a resistant clone from a heterogeneous population of cells.
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收藏
页码:52 / 59
页数:8
相关论文
共 30 条
  • [1] Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750
    Barchiesi, F
    Calabrese, D
    Sanglard, D
    Di Francesco, LF
    Caselli, F
    Giannini, D
    Giacometti, A
    Gavaudan, S
    Scalise, G
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (06) : 1578 - 1584
  • [2] Reversible fluconazole resistance in Candida albicans: A potential in vitro model
    Calvet, HM
    Yeaman, MR
    Filler, SG
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (03) : 535 - 539
  • [3] Methicillin resistance in staphylococci: Molecular and biochemical basis and clinical implications
    Chambers, HF
    [J]. CLINICAL MICROBIOLOGY REVIEWS, 1997, 10 (04) : 781 - +
  • [4] Evolution of drug resistance in experimental populations of Candida albicans
    Cowen, LE
    Sanglard, D
    Calabrese, D
    Sirjusingh, C
    Anderson, JB
    Kohn, LM
    [J]. JOURNAL OF BACTERIOLOGY, 2000, 182 (06) : 1515 - 1522
  • [5] A 10-MINUTE DNA PREPARATION FROM YEAST EFFICIENTLY RELEASES AUTONOMOUS PLASMIDS FOR TRANSFORMATION OF ESCHERICHIA-COLI
    HOFFMAN, CS
    WINSTON, F
    [J]. GENE, 1987, 57 (2-3) : 267 - 272
  • [6] Transcriptional analyses of antifungal drug resistance in Candida albicans
    Lyons, CN
    White, TC
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (09) : 2296 - 2303
  • [7] Maniatis T., 1982, MOL CLONING A LAB MA
  • [8] Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans
    Marichal, P
    Koymans, L
    Willemsens, S
    Bellens, D
    Verhasselt, P
    Luyten, W
    Borgers, M
    Ramaekers, FCS
    Odds, FC
    Vanden Bossche, H
    [J]. MICROBIOLOGY-SGM, 1999, 145 : 2701 - 2713
  • [9] Rapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR
    Marr, KA
    Lyons, CN
    Rustad, T
    Bowden, RA
    White, TC
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1998, 42 (10) : 2584 - 2589
  • [10] Development of fluconazole resistance in Candida albicans causing disseminated infection in a patient undergoing marrow transplantation
    Marr, KA
    White, TC
    vanBurik, JAH
    Bowden, RA
    [J]. CLINICAL INFECTIOUS DISEASES, 1997, 25 (04) : 908 - 910