Inactivation of sterol Δ5,6-desaturase attenuates virulence in Candida albicans

Antimicrobial Agents and Chemotherapy

Volumn 49, Issue 9, 2005, Pages 3646-3651

  Chau, Andrew S ^a   Gurnani, Maya ^a   Hawkinson, Robyn ^a   Laverdiere, Michel ^b   Cacciapuoti, Anthony ^a   McNicholas, Paul M ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b MAISONNEUVE ROSEMONT HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHOTERICIN B; ERGOSTEROL; FLUCONAZOLE; FUNGAL ENZYME; FUNGAL PROTEIN; ITRACONAZOLE; POSACONAZOLE; PROTEIN ERG3; PYRROLE DERIVATIVE; STEROL; STEROL DELTA 5,6 DESATURASE; UNCLASSIFIED DRUG; VORICONAZOLE; ANTIFUNGAL AGENT; ENZYME INHIBITOR; FUNGAL DNA; OXIDOREDUCTASE; STEROL DELTA 5 DESATURASE; STEROL DELTA-5 DESATURASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; CANDIDA ALBICANS; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INACTIVATION; ERG3 GENE; FUNGAL GENE; FUNGAL STRAIN; FUNGAL VIRULENCE; FUNGUS CULTURE; FUNGUS ISOLATION; GENE DELETION; HOMOZYGOSITY; MALE; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MYCOSIS; NONHUMAN; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; STEROL SYNTHESIS; WILD TYPE; ANIMAL; BIOSYNTHESIS; CANDIDIASIS; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; GENETICS; GENOTYPE; KIDNEY; MICROBIOLOGICAL EXAMINATION; MICROBIOLOGY; MUTATION; PATHOGENICITY; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; ANTIFUNGAL AGENTS; AZOLES; CANDIDA ALBICANS; CANDIDIASIS; DNA, FUNGAL; DRUG RESISTANCE, FUNGAL; ENZYME INHIBITORS; GENOTYPE; KIDNEY; MICE; MICROBIAL SENSITIVITY TESTS; MUTATION; OXIDOREDUCTASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 24144444094     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.49.9.3646-3651.2005     Document Type: Article

References (21)

1. Chau, A. S., C. A. Mendrick, F. J. Sabatelli, Loebenberg, and D. P. M. McNicholas. 2004. Application of real-time quantitative PCR to the molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob. Agents Chemother. 48:2124-2131.
2. Cowen, L. E., D. Sanglard, D. Calabrese, C. Sirjusingh, J. B. Anderson, and L. M. Kohn. 2000. Evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 182:1515-1522.
3. Favre, B., M. Didmon, and N. S. Ryder. 1999. Multiple amino acid substitutions in lanosterol 14alpha-demethylase contribute to azole resistance in Candida albicans. Microbiology 145:2715-2725.
4. Ha, K. C., and T. C. White. 1999. Effects of azole antifungal drugs on the transition from yeast cells to hyphae in susceptible and resistant isolates of the pathogenic yeast Candida albicans. Antimicrob. Agents Chemother. 43:763-768.
5. Kakeya, H., Y. Miyazaki, H. Miyazaki, K. Nyswaner, B. Grimberg, and J. E, Bennett. 2000. Genetic analysis of azoic resistance in the Darlington strain of Candida albicans. Antimicrob. Agents Chemother. 44:2985-2990.
6. 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.
7. Li, X., N, Brown, A. S. Chau, J. L. López-Ribot, C. A. Mendrick, D. Loebenberg, R. S. Hare, B. J. DiDomenico, and P. M. McNicholas. 2004. Changes in susceptibility to posaconazole (POS) in clinical isolates of Candida albicans. J. Antimicrob. Chemother. 53:74-80.
8. Marichal, P., L. Koymans, S. Willemsens, D. Bellens, P. Verhasselt, W. Luyten, M. Borgers, F. C. Ramaekers, F. C. Odds, and H. V. Bossche. 1999b. Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p. Cyp51p) to azole resistance in Candida albicans. Microbiology 145:2701-2713.
9. Martin, S. W., and J. B. Konopka. 2004. Lipid raft polarization contributes to hyphal growth in Candida albicans. Eukaryot. Cell 3:675-684.
10. Miwa, T., Y. Takagi, M. Shinozaki, C. W. Yun, W. A. Schell, J. R. Perfect, H. Kumagai, and H. Tamaki. 2004. Gpr1, a putative G-protein-coupled receptor, regulates morphogenesis and hypha formation in the pathogenic fungus Candida albicans. Eukaryot. Cell 3:919-931.
11. Munayyer, H., A. S. Chau, P. A. Mann, T. Yarosh-Tomaine, L. Heimark, K. J. Shaw, R. S. Hare, J. Greene, R. E. Palermo, and P. M. McNicholas. 2004. Posaconazole is a potent inhibitor of sterol 14α-demethylation in yeasts and molds. Antimicrob. Agents Chemother. 48:3690-3696.
12. National Committee for Clinical Laboratory Standards. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard. Document M27-A2. National Committee for Clinical Laboratory Standards, Wayne, Pa.
13. Nolle, F. S., T. Parkinson, D. J. Falconer, S. Dix, J. Williams, C. Gilmore, R. Geller, and J. R. Wingard. 1997. Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob. Agents Chemother. 41:196-199.
14. Odds, F. C., A. J. Brown, and N. A. Gow. 2003. Antifungal agents: mechanisms of action. Trends Microbiol. 11:272-279.
15. Perea, S., J. L. Lopez-Ribot, W. R. Kirkpatrick, R. K. McAtee, R. A. Santillan, M. Martinez, D. Calabrese, D. Sanglard, and T. F. Patterson. 2001. Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients. Antimicrob. Agents Chemother. 45:2676-2684.
16. Sanglard, D., F. Ischer, L. Koymans, and J. Bille. 1998. Amino acid substitutions in the cytochrome P-450 lanosterol 14α-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents. Antimicrob. Agents Chemother. 42:241-253.
17. Sanglard, D., and F. C. Odds. 2002. Resistance of Candida species to antifungal agents: molecular mechanism and clinical consequences. Lancet Infect. Dis. 2:73-85.
18. 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.
19. Saville, S. P., A. L. Lazzell, C. Monteagudo, and J. L. Lopez-Ribot. 2004. Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot. Cell 2:1053-1060.
20. Vanden Bossche, H. 1985. Biochemical targets for antifungal azole derivatives: hypothesis on the mode of action. Curr. Top. Med. Mycol. 1:313-351.
21. White, T. C. S. Holleman, F. Dy, F. D. Mirels, and D. A. Stevens. 2002. Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob. Agents Chemother. 46:1704-1713.