Substitutions at methionine 220 in the 14α-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs

被引:164
作者
Mellado, E [1 ]
Garcia-Effron, G [1 ]
Alcazar-Fuoli, L [1 ]
Cuenca-Estrella, M [1 ]
Rodriguez-Tudela, JL [1 ]
机构
[1] Inst Salud Carlos III, Serv Microl, Ctr Nacl Microbiol, Madrid 28220, Spain
关键词
D O I
10.1128/AAC.48.7.2747-2750.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (cyp51A and cyp51B) encoding the 14alpha-sterol demethylases revealed that all five strains harbored mutations in cyp51A resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transformants exhibited reduced susceptibility to all triazole agents, confirming that the mutations were responsible for the resistance phenotype.
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页码:2747 / 2750
页数:4
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共 32 条
  • [1] In vitro susceptibility of respiratory isolates of Aspergillus species to itraconazole and amphotericin B. Acquired resistance to itraconazole
    Chryssanthou, E
    [J]. SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, 1997, 29 (05) : 509 - 512
  • [2] Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus
    Cuenca-Estrella, M
    Rodríguez-Tudela, JL
    Mellado, E
    Martínez-Suárez, JV
    Monzón, A
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1998, 42 (04) : 531 - 533
  • [3] In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis
    Dannaoui, E
    Borel, E
    Persat, F
    Monier, MF
    Piens, MA
    [J]. JOURNAL OF MEDICAL MICROBIOLOGY, 1999, 48 (12) : 1087 - 1093
  • [4] In-vitro susceptibility of Aspergillus spp. isolates to amphotericin B and itraconazole
    Dannaoui, E
    Persat, F
    Monier, MF
    Borel, E
    Piens, MA
    Picot, S
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1999, 44 (04) : 553 - 555
  • [5] PCR cloning and detection of point mutations in the eburicol 14α-demethylase (CYP51) gene from Erysiphe graminis f. sp. hordei, a "recalcitrant" fungus
    Délye, C
    Bousset, L
    Corio-Costet, MF
    [J]. CURRENT GENETICS, 1998, 34 (05) : 399 - 403
  • [6] Delye C, 1997, APPL ENVIRON MICROB, V63, P2966
  • [7] Itraconazole resistance in Aspergillus fumigatus
    Denning, DW
    Venkateswarlu, K
    Oakley, KL
    Anderson, MJ
    Manning, NJ
    Stevens, DA
    Warnock, DW
    Kelly, SL
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (06) : 1364 - 1368
  • [8] Correlation between in-vitro susceptibility testing to itraconazole and in-vivo outcome of Aspergillus fumigatus infection
    Denning, DW
    Radford, SA
    Oakley, KL
    Hall, L
    Johnson, EM
    Warnock, DW
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1997, 40 (03) : 401 - 414
  • [9] A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus
    Diaz-Guerra, TM
    Mellado, E
    Cuenca-Estrella, M
    Rodriguez-Tudela, JL
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (03) : 1120 - 1124
  • [10] Multiple amino acid substitutions in lanosterol 14α-demethylase contribute to azole resistance in Candida albicans
    Favre, B
    Didmon, M
    Ryder, NS
    [J]. MICROBIOLOGY-SGM, 1999, 145 : 2715 - 2725