Multiple amino acid substitutions in lanosterol 14α-demethylase contribute to azole resistance in Candida albicans

Microbiology

Volumn 145, Issue 10, 1999, Pages 2715-2725

  Favre, Bertrand ^a,b   Didmon, Mark ^a   Ryder, Neil S ^a  

^a NOVARTIS RESEARCH INSTITUTE   (Austria)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Azoles; Candida albicans; Fluconazole resistance; Lanosterol 14 demethylase

Indexed keywords

ANTIFUNGAL AGENT; FLUCONAZOLE; LANOSTEROL;

AMINO ACID SUBSTITUTION; ARTICLE; CANDIDA ALBICANS; CARBOXY TERMINAL SEQUENCE; CROSS RESISTANCE; DRUG RESISTANCE; FUNGAL GENETICS; FUNGUS MUTATION; GENE SEQUENCE; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR CLONING; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; SACCHAROMYCES CEREVISIAE; WESTERN BLOTTING;

CANDIDA ALBICANS;

EID: 0032880113     PISSN: 13500872     EISSN: None     Source Type: Journal    
DOI: 10.1099/00221287-145-10-2715     Document Type: Article

References (72)

1. Alarco, A. M., Balan, I., Talibi, D., Mainville, N. & Raymond, M. (1997). AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1, encoding a transporter of the major facilitator superfamily. J Biol Chem 272, 19304-19313.
2. Albertson, G. D., Niimi, M., Cannon, R. D. & Jenkinson, H. F. (1996). Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrob Agents Chemother 40, 2835-2841.
3. 14DM (lanosterol 14α-demethylase) from yeast, evidence confirming the intermediate step of lanosterol 14α-demethylase. J Biol Chem 264, 18502-18505.
4. Barchiesi, F., Difrancesco, L. F., Compagnucci, P., Arzeni, D., Giacometti, A. & Scalise, G. (1998). In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans. J Antimicrob Chemother 41, 59-65.
5. Becker, D. M. & Guarente, L. (1991). High-efficiency transformation of yeast by electroporation. Methods Enzymol 194, 182-187.
6. Boscott, P. E. & Grant. G. H. (1994). Modeling cytochrome P450 14α-demethylase (Candida albicans) from P450cam. J Mol Graphics 12, 185-192.
7. Chen, C., Kalb, V. F., Turi, T. G. & Loper, J. C. (1988). Primary structure of the cytochrome P450 lanosterol 14α-demethylase gene from Candida tropicalis. DNA 7, 617-626.
8. Denning, D. W., Baily, G. G. & Hood, S. V. (1997). Azole resistance in Candida. Eur J Clin Microbiol Infect Dis 16, 261-280.
9. Doignon, F., Aigle, M. & Ribereaugayon, P. (1993). Resistance to imidazoles and triazoles in Saccharomyces cerevisiae as a new dominant marker. Plasmid 30, 224-233.
10. Favre, B. & Ryder, N. S. (1996). Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents. Antimicrob Agents Chemother 40, 443-447.
11. Favre, B. & Ryder, N. S. (1997a). Cloning and expression of squalene epoxidase from the pathogenic yeast Candida albicans. Gene 189, 119-126.
12. Favre, B. & Ryder, N. S. (1997b). Differential inhibition of fungal and mammalian squalene epoxidases by the benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine. Arch Biochem Biophys 340, 265-269.
13. Feczcko, J. M. (1992). 17. Overview of fluconazole. In Recent Progress in Antifungal Therapy, pp. 191-201. Edited by H. Yamaguchi, G. S. Kobayashi & H. Takahashi, New York: Marcel Dekker.
14. Galgiani, J. N., Bartlett, M. S., Ghannoum, M. A., Espinell-Ingroff, A., Lancaster, M. V., Odds, F. C., Pfaller, M. A., Rex, J. H. & Rinaldi, M. G. (1995). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Tentative Standard. Wayne, PA: NCCLS.
15. Ghannoum, M. A., Rex, J. H. & Galgiani, J. N. (1996). Susceptibility-testing of fungi: current status of correlation of in vitro data with clinical outcome. J Clin Microbiol 34, 489-495.
16. r gene. Antimicrob Agents Chemother 39, 422-426.
17. Hitchcock, C. A. (1993). 15. Chemistry and mode of action of fluconazole. In Cutaneous Antifungal Agents. Selected Compounds in Clinical Practice and Development, pp. 183-197. Edited by J. W. Rippon & R. A. Fromtling, New York: Marcel Dekker.
18. Hitchcock, C. A., Dickinson, K., Brown, S. B., Evans, E. G. V. & Adams, D. J. (1989). Purification and properties of cytochrome P-450-dependent 14α-sterol demethylase from Candida albicans. Biochem J 263, 573-579.
19. Hitchcock, C. A., Dickinson, K., Brown, S. B., Evans, E. G. V. & Adams, D. J. (1990). Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14α-sterol demethylase purified from Candida albicans. Biochem J 266, 475-480.
20. SG1: complete primary structures deduced from cloned DNAs. Biochem Biophys Res Commun 155, 317-323.
21. Joseph-Home, T., Hollomon, D., Loeffler, R. S. T. & Kelly, S. L. (1995). Altered P450 activity associated with direct selection for fungal azole resistance. FEBS Lett 374, 174-178.
22. Kalb, V. F., Loper, J. C., Dey, C. R., Woods, C. W. & Sutter, T. R. (1986). Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae. Gene 45, 237-245.
23. Kelly, S. L., Arnoldi, A. & Kelly, D. E. (1993). Molecular genetic analysis of azole antifungal mode of action. Biochem Soc Trans 21, 1034-1038.
24. Kelly, S. L., Lamb, D. C., Kelly, D. E., Manning, N. J., Loeffler, J., Hebart, H., Schumacher, U. & Einsele, H. (1997). Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol Δ(5,6)-desaturation. FEBS Lett 400, 80-82.
25. Lai, M. H. & Kirsch, D. R. (1989). Nucleotide sequence of cytochrome P450 L1A1 (lanosterol 14α-demethylase) from Candida albicans. Nucleic Acids Res 17, 804.
26. Lamb, D. C., Corran, A., Baldwin, B. C., Kwonchung, J. & Kelly, S. L. (1995). Resistant P45051A1 activity in azole antifungal tolerant Cryptococcus neoformans from AIDS patients. FEBS Lett 368, 326-330.
27. Lamb, D. C., Kelly, D. E., Schunck, W. H., Shyadehi, A. Z., Akhtar, M., Lowe, D. J., Baldwin, B. C. & Kelly, S. L. (1997). The mutation T315A in Candida albicans sterol 14α-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. J Biol Chem 272, 5682-5688.
28. Law, D., Moore, C. B., Wardle, H. M., Ganguli, L. A., Keaney, M. G. L. & Denning, D. W. (1994). High prevalence of antifungal resistance in Candida spp. from patients with AIDS. J Antimicrob Chemother 34, 659-668.
29. Loeffler, J., Kelly, S. L., Hebart, H., Schumacher, U., Lassflorl, C. & Einsele, H. (1997). Molecular analysis of cyp51 from fluconazole-resistant Candida albicans strains. FEMS Microbiol Lett 151, 263-268.
30. Lopez-Ribot, J. L., Mcatee, R. K., Lee, L. N., Kirkpatrick, W. R., White, T. C., Sanglard, D. & Patterson, T. F. (1998). Distinct patterns of gene expression associated with development of fluconazole resistance in serial Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob Agents Chemother 42, 2932-2937.
31. Marichal, P., Gorrens, J., Coene, M. C., Lejeune, L. & Vandenbossche, H. (1995). Origin of differences in susceptibility of Candida krusei to azole antifungal agents. Mycoses 38, 111-117.
32. Miyazaki, H., Miyazaki, Y., Geber, A., Parkinson, T., Hitchcock, C., Falconer, D. J., Ward, D. J., Marsden, K. & Bennett, J. E. (1998). Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrob Agents Chemother 42, 1695-1701.
33. Moran, G. P., Sanglard, D., Donnelly, S. M., Shanley, D. B., Sullivan, D. J. & Coleman, D. C. (1998). Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob Agents Chemother 42, 1819-1830.
34. Orozco, A. S., Higginbotham, L. M., Hitchcock, C. A., Parkinson, T., Falconer, D., Ibrahim, A. S., Ghannoum, M. A. & Filler, S. G. (1998). Mechanism of fluconazole resistance in Candida krusei. Antimicrob Agents Chemother 42, 2645-2649.
35. Parkinson, T., Falconer, D. J. & Hitchcock, C. A. (1995). Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. Antimicrob Agents Chemother 39, 1696-1699.
36. Philippsen, P., Stotz, A. & Scherf, C. (1991). DNA of Saccharomyces cerevisiae. Methods Enzymol 194, 169-182.
37. Poulos, T. L., Finzel, B. C. & Howard, A. J. (1987). High-resolution crystal structure of cytochrome P450cam. J Mol Biol 195, 687-700.
38. Prasad, R., Dewergifosse, P., Goffeau, A. & Balzi, E. (1995). Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr Genet 27, 320-329.
39. Rex, J. H., Rinaldi, M. G. & Pfaller, M. A. (1995). Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 39, 1-8.
40. Rex, J. H., Pfaller, M. A., Lancaster, M., Odds, F. C., Bolmstrom, A. & Rinaldi, M. G. (1996). Quality control guidelines for National Committee for clinical laboratory standards - recommended broth macrodilution testing of ketoconazole and itraconazole. J Clin Microbiol 34, 816-817.
41. Rinaldi, M. G. (1993). 1. Biology and pathogenicity of Candida species. In Candidiasis. Pathogenesis, Diagnosis, and Treatment, pp. 1-20. Edited by G. P. Bodey. New York: Raven Press.
42. Ryder, N. S. (1985). Specific inhibition of fungal sterol biosynthesis by SF 86-327, a new allylamine antimycotic agent. Antimicrob Agents Chemother 27, 252-256.
43. Ryder, N. S. (1987). Squalene epoxidase as the target of antifungal allylamines. Pestic Sci 21, 281-288.
44. Ryder, N. S. & Favre, B. (1997). Antifungal activity and mechanism of action of terbinafine. Rev Contemp Pharmacother 8, 275-287.
45. Ryder, N. S., Seidl, G. & Troke, P. F. (1984). Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans. Antimicrob Agents Chemother 25, 483-487.
46. Ryder, N. S., Wagner, S. & Leitner, I. (1998). In vitro activities of terbinafine against cutaneous isolates of Candida albicans and other pathogenic yeasts. Antimicrob Agents Chemother 42, 1057-1061.
47. Ryley, J. F., Wilson, R. G. & Barrett-Bee, K. J. (1984). Azole resistance in Candida albicans. Sabouraudia 22, 53-63.
48. Sanglard, D., Sengstag, C. & Seghezzi, W. (1993). Probing the membrane topology of Candida tropicalis cytochrome P450. Eur J Biochem 216, 477-485.
49. Sanglard, D., Kuchler, K., Ischer, F., Pagani, J. L., Monod, M. & Bille, J. (1995). Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother 39, 2378-2386.
50. Sanglard, D., Ischer, F., Monod, M. & Bille, J. (1996). Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob Agents Chemother 40, 2300-2305.
51. Sanglard, D., Ischer, F., Monod, M. & Bille, J. (1997). Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143, 405-416.
52. Sanglard, D., Ischer, F., Koymans, L. & Bille, J. (1998). Amino acid substitutions in the cytochrome P-450 lanosterol 14 alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob Agents Chemother 42, 241-253.
53. Santos, M. A. S. & Tuite, M. F. (1995). The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res 23, 1481-1486.
54. Shyadehi, A. Z., Lamb, D. C., Kelly, S. L., Kelly, D. E., Schunck, W. H., Wright, J. N., Corina, D. & Akhtar, M. (1996). The mechanism of the acyl-carbon bond cleavage reaction catalyzed by recombinant sterol 14α-demethylase of Candida albicans (other names are: lanosterol 14α-demethylase, P-450(14DM), and CYP51). J Biol Chem 271, 12445-12450.
55. Sutter, T. R. & Loper, J. C. (1989). Disruption of Saccharomyces cerevisiae gene for NADPH-cytochrome P450 reductase causes increased sensitivity to ketoconazole. Biochem Biophys Res Commun 160, 1257-1266.
56. Thompson, J. D., Higgins, D. G. & Gibson, T. J. (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22, 4673-4680.
57. 5-encoding gene which suppresses ketoconazole hypersensitivity in a NADPH-P-450 reductase-deficient strain. Gene 142, 123-127.
58. Tumbarello, M., Caldarola, G., Tacconelli, E., Morace, G., Posteraro, B., Cauda, R. & Ortona, L. (1996). Analysis of the risk factors associated with the emergence of azole resistant oral candidosis in the course of HIV infection. J Antimicrob Chemother 38, 691-699.
59. Vanden Bossche, H. & Koymans, L. (1998). Cytochromes P450 in fungi. Mycoses 41, Suppl. 1, 32-38.
60. Vanden Bossche, H. & Marichal, P. (1992). 3. Azole antifungals: mode of action. In Recent Progress in Antifungal Chemotherapy, pp. 25-40. Edited by H. Yamaguchi, G. S. Kobayashi & H. Takahashi. New York: Marcel Dekker.
61. Vanden Bossche, H., Marichal, P., Gorrens, J., Bellens, D., Moereels, H. & Janssen, P. A. J. (1990). Mutation in cytochrome P-450-dependent 14α-demethylase results in decreased affinity for azole antifungals. Biochem Soc Trans 18, 56-59.
62. Vanden Bossche, H., Marichal, P., Odds, F. C., Le Jeune, L. & Coene, M. C. (1992). Characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother 36, 2602-2610.
63. Vanden Bossche, H., Marichal, P. & Odds, F. C. (1994). Molecular mechanisms of drug resistance in fungi. Trends Microbiol 2, 393-400.
64. van Veen, H. W. & Konings, W. N. (1998). The ABC family of multidrug transporters in microorganisms. Biochim Biophys Acta 1365, 31-36.
65. Venkateswarlu, K., Denning. D. W., Manning, N. J. & Kelly, S. L. (1996). Reduced accumulation of drug in Candida krusei accounts for itraconazole resistance. Antimicrob Agents Chemother 40, 2443-2446.
66. Venkateswarlu, K., Taylor, M., Manning, N. J., Rinaldi, M. G. & Kelly, S. L. (1997). Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother 41, 748-751.
67. 5 in yeast results in marked proliferation of the intracellular membrane. J Cell Sci 106, 249-259.
68. White, T. C. (1997a). Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immuno-deficiency virus. Antimicrob Agents Chemother 41, 1482-1487.
69. White, T. C. (1997b). The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14α demethylase in Candida albicans. Antimicrob Agents Chemother 41, 1488-1494.
70. White, T. C., Marr, K. A. & Bowden, R. A. (1998). Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 11, 382-402.
71. Yoshida, M. & Aoyama, Y. (1985). Interaction of azole fungicides with yeast cytochrome P-450 which catalyzes lanosterol 14α-demethylation. In In Vitro and In Vivo Evaluation of Antifungal Agents, pp. 123-134. Edited by K. Iwata & H. Vanden Bossche. Amsterdam: Elsevier.
72. Zimmer, T., Vogel, F., Ohta, A., Takagi, M. & Schunck, W. H. (1997). Protein quality - a determinant of the intracellular fate of membrane-bound cytochromes P450 in yeast. DNA Cell Biol 16, 501-514.