Correlation between rhodamine 123 accumulation and atole sensitivity in Candida species: Possible role for drug efflux in drug resistance

被引:80
作者
Clark, FS
Parkinson, T
Hitchcock, CA
Gow, NAR
机构
[1] UNIV ABERDEEN, MARISCHAL COLL, DEPT MOLEC & CELL BIOL, ABERDEEN AB9 1AS, SCOTLAND
[2] PFIZER LTD, CENT RES, DEPT DISCOVERY BIOL, SANDWICH CT13 9NJ, KENT, ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1128/AAC.40.2.419
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A wide variety of prokaryotic and eukaryotic cells exhibit a multidrug resistance (MDR) phenotype, indicating that resistance to potentially toxic compounds is mediated by their active efflux from the cell. We have sought to determine whether resistance to azoles in some strains of Candida species may be due in part to active drug efflux. Rhodamine 123 (Rh123) is a fluorescent compound that is transported by a wide variety of MDR cell types, We have shown that certain azole-resistant strains of Candida albicans, C. glabrata, and C. krusei accumulate less Rh123 than azole-susceptible ones, In C. albicans, Rh123 accumulation was growth phase and temperature dependent and was increased by proton uncouplers and by reserpine, an MDR modulator, This is consistent with an energy-dependent efflux mechanism for Rh123, mediated by an MDR transporter, In C. glabrata, but not in C. albicans, there was competition between Rh123 and fluconazole for efflux. Thus, in C. glabrata, Rh123 and fluconazole appear to be transported via a common MDR-like transporter, whereas in C. albicans, the Rh123 transporter does not appear to transport azoles.
引用
收藏
页码:419 / 425
页数:7
相关论文
共 56 条
  • [1] AMBUDKAR SV, 1992, P NATL ACAD SCI USA, V89, pS472
  • [2] AOKI S, 1982, PLANT CELL PHYSIOL, V23, P721
  • [3] AOKI S, 1985, JPN J ORAL BIOL, V27, P737
  • [4] BALZI E, 1994, J BIOL CHEM, V269, P2206
  • [5] GENETICS AND BIOCHEMISTRY OF YEAST MULTIDRUG-RESISTANCE
    BALZI, E
    GOFFEAU, A
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1994, 1187 (02): : 152 - 162
  • [6] MULTIPLE OR PLEIOTROPIC DRUG-RESISTANCE IN YEAST
    BALZI, E
    GOFFEAU, A
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1073 (02) : 241 - 252
  • [7] Barrett-Bee K., 1992, Emerging targets in antibacterial and antifungal chemotherapy, P410, DOI DOI 10.1007/978-1-4615-3274-3_16
  • [8] CANDIDA-ALBICANS GENE ENCODING RESISTANCE TO BENOMYL AND METHOTREXATE IS A MULTIDRUG-RESISTANCE GENE
    BENYAACOV, R
    KNOLLER, S
    CALDWELL, GA
    BECKER, JM
    KOLTIN, Y
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (04) : 648 - 652
  • [9] RHODAMINE-123 SELECTIVELY REDUCES CLONAL GROWTH OF CARCINOMA-CELLS INVITRO
    BERNAL, SD
    LAMPIDIS, TJ
    SUMMERHAYES, IC
    CHEN, LB
    [J]. SCIENCE, 1982, 218 (4577) : 1117 - 1119
  • [10] INDUCTION BY VERAPAMIL OF A RAPID INCREASE IN ATP CONSUMPTION IN MULTIDRUG-RESISTANT TUMOR-CELLS
    BROXTERMAN, HJ
    PINEDO, HM
    KUIPER, CM
    KAPTEIN, LCM
    SCHUURHUIS, GJ
    LANKELMA, J
    [J]. FASEB JOURNAL, 1988, 2 (07) : 2278 - 2282