Aspergillus fumigatus C-5 sterol desaturases Erg3A and Erg3B: Role in sterol biosynthesis and antifungal drug susceptibility

Antimicrobial Agents and Chemotherapy

Volumn 50, Issue 2, 2006, Pages 453-460

  Alcazar Fuoli, Laura ^a   Mellado, Emilia ^a   Garcia Effron, Guillermo ^a   Buitrago, Maria J ^a   Lopez, Jordi F ^b   Grimalt, Joan O ^b   Cuenca Estrella, J Manuel ^a   Rodriguez Tudela, Juan L ^a  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

^b CSIC   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ANTIFUNGAL AGENT; C 5 STEROL DESATURASE ERG3A; C 5 STEROL DESATURASE ERG3B; ERGOSTEROL; FLUCONAZOLE; FUNGAL ENZYME; ITRACONAZOLE; KETOCONAZOLE; NUCLEOTIDE; UNCLASSIFIED DRUG; VORICONAZOLE;

ANTIBIOTIC SENSITIVITY; ARTICLE; ASPERGILLUS FUMIGATUS; CELL VIABILITY; CONTROLLED STUDY; ENZYME ACTIVITY; ERG3A GENE; ERG3B GENE; FUNGUS ISOLATION; FUNGUS MUTANT; FUNGUS MUTATION; GENE; GENE REPLICATION; KNOCKOUT GENE; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; NUCLEOTIDE SEQUENCE; NULL ALLELE; PHENOTYPE; PRIORITY JOURNAL; SEQUENCE ANALYSIS; STEROL SYNTHESIS;

ASPERGILLUS FUMIGATUS; MICROBIAL SENSITIVITY TESTS; OXIDOREDUCTASES; STEROLS;

EID: 31944434501     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.50.2.453-460.2006     Document Type: Article

References (50)

1. Arthington, B. A., L. G. Bennett, P. L. Skatrud, C. J. Guynn, R. J. Barbuch, C. E. Ulbright, and M. Bard. 1991. Cloning, disruption and sequence of the gene encoding yeast C-5 sterol desaturase. Gene 102:39-44.
2. Arthington-Skaggs, B. A., D. W. Warnock, and C. J. Morrison. 2000. Quantitation of Candida albicans ergosterol content improves the correlation between in vitro antifungal susceptibility test results and in vivo outcome after fluconazole treatment in a murine model of invasive candidiasis. Antimicrob. Agents Chemother. 44:2081-2085.
3. Bard, M., N. D. Lees, T. Turi, D. Craft, L. Cofrin, R. Barbuch, C. Koegel, and J. C. Loper. 1993. Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase) mutations in Saccharomyces cerevisiae and Candida albicans. Lipids 28:963-967.
4. Chryssanthou, E. 1997. In vitro susceptibility of respiratory isolates of Aspergillus species to itraconazole and amphotericin B acquired resistance to itraconazole. Scand. J. Infect. Dis. 29:509-512.
5. Clinical and Laboratory Standards Institute. 2005. Reference method for broth dilution antifungal susceptibility. Testing of filamentous fungi. Approved standard document M38-A. Clinical and Laboratory Standards Institute, Wayne, Pa.
6. Cove, D. J. 1966. The induction and repression of nitrate reductase in the fungus Aspergillus nidulans. Biochim. Biophys. Acta 113:51-56.
7. Cuenca-Estrella, M., T. M. Diaz-Guerra, E. Mellado, and J. L. Rodriguez-Tudela. 2001. Influence of glucose supplementation and inoculum size on growth kinetics and antifungal susceptibility testing of Candida spp. J. Clin. Microbiol. 39:525-532.
8. Cullen, D., S. A. Leong, L. J. Wilson, and D. J. Henner. 1987. Transformation of Aspergillus nidulans with the hygromycin-resistance gene, hph. Gene 57:21-26.
9. Dannaoui, E., E. Borel, M. F. Monier, M. A. Piens, S. Picot, and F. Persat. 2001. Acquired itraconazole resistance in Aspergillus fumigatus. J. Antimicrob. Chemother. 47:333-340.
10. Dannaoui, E., E. Borel, F. Persat, M. F. Monier, M. A. Piens, et al. 1999. In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. J. Med. Microbiol. 48:1087-1093.
11. Denning, D. W., K. Venkateswarlu, K. L. Oakley, M. J. Anderson, N. J. Manning, D. A. Stevens, D. W. Warnock, and S. L. Kelly. 1997. Itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 41:1364-1368.
12. Diaz-Guerra, T. M., E. Mellado, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2003. A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 47:1120-1124.
13. Ferreira, M. E., A. L. Colombo, I. Paulsen, Q. Ren, J. Wortman, J. Huang, M. H. Goldman, and G. H. Goldman. 2005. The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus. Med. Mycol. 43(Suppl. 1):S313-S319.
14. Fryberg, M., A. C. Oehlschlager, and A. M. Unrau. 1973. Biosynthesis of ergosterol in yeast. Evidence for multiple pathways. J. Am. Chem. Soc. 95:5747-5757.
15. Geber, A., C. A. Hitchcock, J. E. Swartz, F. S. Pullen, K. E. Marsden, K. J. Kwon-Chung, and J. E. Bennett. 1995. Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell viability, cell growth, sterol composition, and antifungal susceptibility. Antimicrob. Agents Chemother. 39:2708-2717.
16. Gomez-Lopez, A., G. Garda-Effron, E. Mellado, A. Monzon, J. L. Rodriguez-Tudela, and M. Cuenca-Estrella. 2003. In vitro activities of three licensed antifungal agents against Spanish clinical isolates of Aspergillus spp. Antimicrob. Agents Chemother. 47:3085-3088.
17. Gooday, G. W. 1995. Cell membrane, p. 62-74. In N. A. R. Gow and G. M. Gadd (ed.), The growing fungus. Chapman & Hall, London, United Kingdom.
18. Gurr, S. J., S. E. Unkles, and J. R. Kinghorn. 1987. The structure and organization of nuclear genes of filamentous fungi, p. 93-139. In J. R. Kinghorn (ed.), Gene structure in eukaryotic microbes. IRL Press, Oxford, United Kingdom.
19. Higgins, D. G., and P. M. Sharp. 1988. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene 73:237-244.
20. Jackson, C. J., D. C. Lamb, N. J. Manning, D. E. Kelly, and S. L. Kelly. 2003. Mutations in Saccharomyces cerevisiae sterol C5-desaturase conferring resistance to the CYP51 inhibitor fluconazole. Biochem. Biophys. Res. Commun. 309:999-1004.
21. Jackson, M. R., T. Nilsson, and P. A. Peterson. 1990. Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J. 9:3153-3162.
22. Johnson, E. M., K. L. Oakley, S. A. Radford, C. B. Moore, P. Warn, D. W. Warnock, and D. W. Denning. 2000. Lack of correlation of in vitro amphotericin B susceptibility testing with outcome in a murine model of Aspergillus infection. J. Antimicrob. Chemother. 45:85-93.
23. Kelly, S. L., D. C. Lamb, D. E. Kelly, J. Loeffler, and H. Einsele. 1996. Resistance to fluconazole and amphotericin in Candida albicans from AIDS patients. Lancet 348:1523-1524.
24. Kelly, S. L., D. C. Lamb, D. E. Kelly, N. J. Manning, J. Loeffler, H. Hebart, U. Schumacher, and H. Einsele. 1997. Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6-desaturation. FEBS Lett. 400:80-82.
25. Kontoyiannis, D. P., and G. P. Bodey. 2002. Invasive aspergillosis in 2002: an update. Eur. J. Clin. Microbiol. Infect. Dis. 21:161-172.
26. Kontoyiannis, D. P., and R. E. Lewis. 2002. Antifungal drug resistance of pathogenic fungi. Lancet 359:1135-1144.
27. Latge, J. P. 1999. Aspergillus fumigatus and aspergillosis. Clin. Microbiol. Rev. 12:310-350.
28. Mann, P. A., R. M. Parmegiani, S. Q. Wei, C. A. Mendrick, X. Li, D. Loebenberg, B. DiDomenico, R. S. Hare, S. S. Walker, and P. M. McNicholas. 2003. Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14α-demethylase. Antimicrob. Agents Chemother. 47:577-581.
29. Mejanelle, L., J. F. Lopez, N. Gunde-Cimerman, and J. O. Grimait. 2001. Ergosterol biosynthesis in novel melanized fungi from hypersaline environments. J. Lipid Res. 42:352-358.
30. Mellado, E., T. M. Diaz-Guerra, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2001. Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J. Clin. Microbiol. 39:2431-2438.
31. Mellado, E., G. Garcia-Effron, L. Alcazar-Fuoli, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2004. Substitutions at methionine 220 in the 14α-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob. Agents Chemother. 48:2747-2750.
32. Miyazaki, Y., A. Geber, H. Miyazaki, D. Falconer, T. Parkinson, C. Hitchcock, B. Grimberg, K. Nyswaner, and J. E. Bennett. 1999. Cloning, sequencing, expression and allelic sequence diversity of ERG3 (C-5 sterol desaturase gene) in Candida albicans. Gene 236:43-51.
33. Mosquera, J., and D. W. Denning. 2002. Azole cross-resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 46:556-557.
34. Nagel, S. B. 2003. Function prediction from protein sequence, p. 65-79 In C. Orengo, D. Jones, and J. Thornton (ed.), Bioinformatics. Genes, proteins and computers. Bios Scientific Publishers, Oxford, United Kingdom.
35. Nascimento, A. M., G. H. Goldman, S. Park, S. A. Marras, G. Delmas, U. Oza, K. Lolans, M. N. Dudley, P. A. Mann, and D. S. Perlin. 2003. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob. Agents Chemother. 47:1719-1726.
36. Petrikkou, E., J. L. Rodriguez-Tudela, M. Cuenca-Estrella, A. Gomez, A. Molleja, and E. Mellado. 2001. Inoculum standardization for antifungal susceptibility testing of filamentous fungi pathogenic for humans. J. Clin. Microbiol. 39:1345-1347.
37. Pinjon, E., G. P. Moran, C. J. Jackson, S. L. Kelly, D. Sanglard, D. C. Coleman, and D. J. Sullivan. 2003. Molecular mechanisms of itraconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 47:2424-2437.
38. Reeslev, M., and A. Kloller. 1995. Comparison of biomass dry weights and radial growth rates of fungal colonies on media solidified with different gelling compounds. Appl. Environ. Microbiol. 61:4236-4239.
39. Rodriguez-Tudela, J. L., E. Chryssanthou, E. Petrikkou, J. Mosquera, D. W. Denning, and M. Cuenca-Estrella. 2003. Interlaboratory evaluation of hematocytometer method of inoculum preparation for testing antifungal susceptibilities of filamentous fungi. J. Clin. Microbiol. 41:5236-5237.
40. Saitou, N., and M. Nei. 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4:406-425.
41. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed., p. 1.21-1.32. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
42. Sanchez, O., and J. Aguirre. 2005. Efficient transformation of Aspergillus nidulans by electroporation of germinated conidia. Fungal Genet. Newslett. 43:48-51.
43. Sanglard, D., F. Ischer, T. Parkinson, D. Falconer, and J. Bille. 2003. Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Antimicrob. Agents Chemother. 47:2404-2412.
44. Slaven, J. W., M. J. Anderson, D. Sanglard, G. K. Dixon, J. Bille, I. S. Roberts, and D. W. Denning. 2002. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet. Biol. 36:199-206.
45. Sugawara, T., Y. Fujimoto, and T. Ishibashi. 2001. Molecular cloning and structural analysis of human sterol C5 desaturase. Biochim. Biophys. Acta 1533:277-284.
46. Tang, C. M., J. Cohen, and D. W. Holden. 1992. An Aspergillus fumigatus alkaline protease mutant constructed by gene disruption is deficient in extracellular elastase activity. Mol. Microbiol. 6:1663-1671.
47. Taton, M., T. Husselstein, P. Benveniste, and A. Rahier. 2000. Role of highly conserved residues in the reaction catalyzed by recombinant Delta7-sterol-C5(6)-desaturase studied by site-directed mutagenesis. Biochemistry 39:701-711.
48. Vallejo, A. N., R. J. Pogulis, and L. R. Pease. 1995. Mutagenesis and synthesis of novel recombinant genes using PCR, p. 603-612. In G. S. Dveksler and C. W. Dieffenbach (ed.), PCR primer: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
49. Weidner, G., C. d'Enfert, A. Koch, P. C. Mol, and A. A. Brakhage. 1998. Development of a homologous transformation system for the human pathogenic fungus Aspergillus fumigatus based on the pyrG gene encoding orotidine 5′-monophosphate decarboxylase. Curr. Genet. 33:378-385.
50. Young, L. Y., C. M. Hull, and J. Heitman. 2003. Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae. Antimicrob. Agents Chemother. 47:2717-2724.