RESISTANT P45051A1 ACTIVITY IN AZOLE ANTIFUNGAL TOLERANT CRYPTOCOCCUS-NEOFORMANS FROM AIDS PATIENTS

被引：48

作者：

LAMB, DC

CORRAN, A

BALDWIN, BC

KWONCHUNG, J

KELLY, SL

机构：

[1] UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,DEPT MOLEC BIOL & BIOTECHNOL,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND

[2] ZENECA AGROCHEM,JEALOTTS HILL RES STN,BRACKNELL,BERKS,ENGLAND

[3] NIH,BETHESDA,MD

来源：

FEBS LETTERS | 1995年 / 368卷 / 02期

基金：

英国惠康基金;

关键词：

CRYPTOCOCCUS; STEROL 14-ALPHA-DEMETHYLASE (P45051A1); AZOLE ANTIFUNGAL; RESISTANCE;

D O I：

10.1016/0014-5793(95)00684-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Azole antifungal compounds are important in the treatment of Cryptococcosis, a major cause of mortality in AIDS patients, The target of the azole drugs is P450 mediated sterol 14 alpha-demethylase. We have investigated the P450 system of Cryptococcus neoformans with respect to azole tolerance observed in clinical isolates which were obtained following the failure of fluconazole therapy. The clinical failure was correlated with in vitro tolerance of azole antifungal when compared to wild-type strains. The microsomal P450 system was typical of yeast and fungi and fluconazole tolerance was not associated with defective sterol biosynthesis. The strains had slightly elevated P450 content and slightly reduced azole levels in the cells, but a clear cause for resistance was the increased level of drug needed to inhibit the sterol 14 alpha-demethylase in vitro.

引用

页码：326 / 330

页数：5

共 24 条

[1] AOYAMA Y, 1983, J BIOL CHEM, V258, P9040
[2] BALLARD SA, 1990, J MED VET MYCOL, V28, P335
[3] ACCUMULATION OF SBI FUNGICIDES IN WILD-TYPE AND FENARIMOL-RESISTANT ISOLATES OF PENICILLIUM-ITALICUM
DEWAARD, MA
VANNISTELROOY, JGM
[J]. PESTICIDE SCIENCE, 1988, 22 (04): : 371 - 382
[4] STEROL COMPOSITION OF CRYPTOCOCCUS-NEOFORMANS IN THE PRESENCE AND ABSENCE OF FLUCONAZOLE
GHANNOUM, MA
SPELLBERG, BJ
IBRAHIM, AS
RITCHIE, JA
CURRIE, B
SPITZER, ED
EDWARDS, JE
CASADEVALL, A
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (09) : 2029 - 2033
[5] RESISTANCE OF CANDIDA-ALBICANS TO AZOLE ANTIFUNGAL AGENTS
HITCHCOCK, CA
[J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (04) : 1039 - 1047
[6] Kelly S. L., 1993, Molecular biology and its application to medical mycology., P199
[7] RESISTANCE TO AMPHOTERICIN-B ASSOCIATED WITH DEFECTIVE STEROL DELTA(8-]7) ISOMERASE IN A CRYPTOCOCCUS-NEOFORMANS STRAIN FROM AN AIDS PATIENT
KELLY, SL
LAMB, DC
TAYLOR, M
CORRAN, AJ
BALDWIN, BC
POWDERLY, WG
[J]. FEMS MICROBIOLOGY LETTERS, 1994, 122 (1-2) : 39 - 42
[8] MOLECULAR-GENETIC ANALYSIS OF AZOLE ANTIFUNGAL MODE OF ACTION
KELLY, SL
ARNOLDI, A
KELLY, DE
[J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (04) : 1034 - 1038
[9] BENZO(A)PYRENE HYDROXYLASE-ACTIVITY IN YEAST IS MEDIATED BY P450 OTHER THAN STEROL 14-ALPHA-DEMETHYLASE
KELLY, SL
LAMB, DC
BALDWIN, BC
KELLY, DE
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 197 (02) : 428 - 432
[10] KELLY SL, 1985, CURRENT GENET, V10, P261

← 1 2 3 →