Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants

Antimicrobial Agents and Chemotherapy

Volumn 50, Issue 4, 2006, Pages 1384-1392

  Tsai, Huei Fung ^a   Krol, Anna A ^a   Sarti, Kelly E ^a   Bennett, John E ^a,b  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CERULENIN; CHLORAMPHENICOL; CYCLOHEXIMIDE; FLUCONAZOLE; ITRACONAZOLE; LEUCINE; PHENYLALANINE; PYRROLE DERIVATIVE; RHODAMINE 6G; SERINE; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PDR1; TRYPTOPHAN; UNCLASSIFIED DRUG; VORICONAZOLE;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; CANDIDA GLABRATA; CGCDR1; CGPDR1 GENE; CULTURE MEDIUM; FUNGAL GENE; FUNGAL STRAIN; FUNGUS CULTURE; FUNGUS ISOLATION; FUNGUS MUTANT; GENE DISRUPTION; GENE EXPRESSION; GENE FUNCTION; MITOCHONDRION; MUTAGENESIS; NONHUMAN; NORTHERN BLOTTING; NUCLEOTIDE SEQUENCE; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN FUNCTION; TRANSPOSON; UPREGULATION;

ANTIFUNGAL AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; BASE SEQUENCE; CANDIDA GLABRATA; CODON; DNA-BINDING PROTEINS; DRUG RESISTANCE, FUNGAL; FLUCONAZOLE; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, FUNGAL; HUMANS; MOLECULAR SEQUENCE DATA; PROMOTER REGIONS (GENETICS); RHODAMINES; SACCHAROMYCES CEREVISIAE; SACCHAROMYCES CEREVISIAE PROTEINS; TRANS-ACTIVATORS;

EID: 33645773419     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.50.4.1384-1392.2006     Document Type: Article

References (44)

1. Balzi, E., W. Chen, S. Ulaszewski, E. Capieaux, and A. Goffeau. 1987. The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. J. Biol. Chem. 262:16871-16879.
2. Bennett, J. E., K. Izumikawa, and K. A. Marr. 2004. Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob. Agents Chemother. 48:1773-1777.
3. Brachmann, C. B., A. Davies, G. J. Cost, E. Caputo, J. Li, P. Hieter, and J. D. Boeke. 1998. Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14:115-132.
4. Brun, S., C. Aubry, O. Lima, R. Filmon, T. Berges, D. Chabasse, and J. P. Bouchara. 2003. Relationships between respiration and susceptibility to azole antifungals in Candida glabrata. Antimicrob. Agents Chemother. 47: 847-853.
5. Brun, S., T. Berges, P. Poupard, C. Vauzelle-Moreau, G. Renier, D. Chabasse, and J. P. Bouchara. 2004. Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob. Agents Chemother. 48:1788-1796.
6. Carvajal, E., H. B. van den Hazel, A. Cybularz-Kolaczkowska, E. Balzi, and A. Goffeau. 1997. Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes. Mol. Gen. Genet. 256:406-415.
7. Defontaine, A., J. P. Bouchara, P. Declerk, C. Planchenault, D. Chabasse, and J. N. Hallet. 1999. In-vitro resistance to azoles associated with mitochondrial DNA deficiency in Candida glabrata. J. Med. Microbiol. 48:663-670.
8. Delahodde, A., T. Delaveau, and C. Jacq. 1995. Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. Mol. Cell. Biol. 15:4043-4051.
9. Delaveau, T., A. Delahodde, E. Carvajal, J. Subik, and C. Jacq. 1994. PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls the multidrug resistance phenomenon. Mol. Gen. Genet. 244:501-511.
10. Devaux, F., E. Carvajal, S. Moye-Rowley, and C. Jacq. 2002. Genome-wide studies on the nuclear PDR3-controlled response to mitochondrial dysfunction in yeast. FEBS Lett. 515:25-28.
11. Dujon, B., D. Sherman, G. Fischer, P. Durrens, S. Casaregola, I. Lafontaine, J. De Montigny, C. Marck, C. Neuveglise, E. Talla, N. Goffard, L. Frangeul, M. Aigle, V. Anthouard, A. Babour, V. Barbe, S. Barnay, S. Blanchin, J. M. Beckerich, E. Beyne, C. Bleykasten, A. Boisrame, J. Boyer, L. Cattolico, F. Confanioleri, A. De Daruvar, L. Despons, E. Fabre, C. Fairhead, H. Ferry-Dumazet, A. Groppi, F. Hantraye, C. Hennequin, N. Jauniaux, P. Joyet, R. Kachouri, A. Kerrest, R. Koszul, M. Lemaire, I. Lesur, L. Ma, H. Muller, J. M. Nicaud, M. Nikolski, S. Oztas, O. Ozier-Kalogeropoulos, S. Pellenz, S. Potier, G. F. Richard, M. L. Straub, A. Suleau, D. Swennen, F. Tekaia, M. Wesolowski-Louvel, E. Westhof, B. Wirth, M. Zeniou-Meyer, I. Zivanovic, M. Bolotin-Fukuhara, A. Thierry, C. Bouchier, B. Caudron, C. Scarpelli, C. Gaillardin, J. Weissenbach, P. Wincker, and J. L. Souciet. 2004. Genome evolution in yeasts. Nature 430:35-44.
12. Hallstrom, T. C., and W. S. Moye-Rowley. 2000. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. J. Biol. Chem. 275:37347-37356.
13. Henry, K. W., J. T. Nickels, and T. D. Edlind. 2000. Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob. Agents Chemother. 44:2693-2700.
14. Izumikawa, K., H. Kakeya, H. F. Tsai, B. Grimberg, and J. E. Bennett. 2003. Function of Candida glabrata ABC transporter gene, PDH1. Yeast 20:249-261.
15. Katzmann, D. J., P. E. Burnett, J. Golin, Y. Mahe, and W. S. Moye-Rowley. 1994. Transcriptional control of the yeast PDR5 gene by the PDR3 gene product. Mol. Cell. Biol. 14:4653-4661.
16. Kaur, R., I. Castano, and B. P. Cormack. 2004. Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Antimicrob. Agents Chemother. 48: 1600-1613.
17. Kelly, S. L., A. Arnoldi, and D. E. Kelly. 1993. Molecular genetic analysis of azole antifungal mode of action. Biochem. Soc. Trans. 21:1034-1038.
18. 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.
19. Kelly, S. L., D. C. Lamb, J. Loeffler, H. Einsele, and D. E. Kelly. 1999. The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity. Biochem. Biophys. Res. Commun. 262:174-179.
20. Kitada, K., E. Yamaguchi, and M. Arisawa. 1996. Isolation of a Candida glabrata centromere and its use in construction of plasmid vectors. Gene 175:105-108.
21. Kolaczkowska, A., M. Kolaczkowski, A. Delahodde, and A. Goffeau. 2002. Functional dissection of Pdr1p, a regulator of multidrug resistance in Saccharomyces cerevisiae. Mol. Genet. Genomics 267:96-106.
22. Lamb, D. C., D. E. Kelly, W. H. Schunck, A. Z. Shyadehi, M. Akhtar, D. J. Lowe, B. C. Baldwin, and S. L. Kelly. 1997. The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. J. Biol. Chem. 272:5682-5688.
23. Lees, N. D., M. Bard, and D. R. Kirsch. 1999. Biochemistry and molecular biology of sterol synthesis in Saccharomyces cerevisiae. Crit. Rev. Biochem. Mol. Biol. 34:33-47.
24. Maesaki, S., P. Marichal, H. Vanden Bossche, D. Sanglard, and S. Kohno. 1999. Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candida albicans strains. J. Antimicrob. Chemother. 44:27-31.
25. Miyazaki, H., Y. Miyazaki, A. Geber, T. Parkinson, C. Hitchcock, D. J. Falconer, D. J. Ward, K. Marsden, and J. E. Bennett. 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.
26. NCCLS. 1995. Reference method for broth dilution antifungal susceptibility testing of yeast. Approved standard M27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.
27. Niimi, M., Y. Nagai, K. Niimi, S. Wada, R. D. Cannon, Y. Uehara, and B. C. Monk. 2002. Identification of two proteins induced by exposure of the pathogenic fungus Candida glabrata to fluconazole. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 782:245-252.
28. 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.
29. Pfaller, M. A., R. N. Jones, G. V. Doern, A. C. Fluit, J. Verhoef, H. S. Sader, S. A. Messer, A. Houston, S. Coffman, R. J. Hollis, and SENTRY Participant Group (Europe). 1999. International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. Diagn. Microbiol. Infect. Dis. 35:19-25.
30. Pfaller, M. A., S. A. Messer, R. J. Hollis, R. N. Jones, and D. J. Diekema. 2002. In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp. Antimicrob. Agents Chemother. 46:1723-1727.
31. Prasad, R., P. De Wergifosse, A. Goffeau, and E. Balzi. 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.
32. Sambrook, J., and W. Russel. 2001. Molecular cloning: a laboratory manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
33. Sanglard, D., F. Ischer, and J. Bille. 2001. Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob. Agents Chemother. 45:1174-1183.
34. Sanglard, D., F. Ischer, D. Calabrese, P. A. Majcherczyk, and J. Bille. 1999. The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob. Agents Chemother. 43:2753-2765.
35. Trick, W. E., S. K. Fridkin, J. R. Edwards, R. A. Hajjeh, and R. P. Gaynes. 2002. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin. Infect. Dis. 35: 627-630.
36. Tsai, H. F., M. Bard, K. Izumikawa, A. A. Krol, A. M. Sturm, N. T. Culbertson, C. A. Pierson, and J. E. Bennett. 2004. Candida glabrata erg1 mutant with increased sensitivity to azoles and to low oxygen tension. Antimicrob. Agents Chemother. 48:2483-2489.
37. Vanden Bossche, H., P. Marichal, J. Gorrens, D. Bellens, H. Moereels, and P. A. Janssen. 1990. Mutation in cytochrome P-450-dependent 14 alpha-demethylase results in decreased affinity for azole antifungals. Biochem. Soc. Trans. 18:56-59.
38. Vermitsky, J. P., and T. D. Edlind. 2004. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob. Agents Chemother. 48:3773-3781.
39. Wada, S., K. Tanabe, A. Yamazaki, M. Niimi, Y. Uehara, K. Niimi, E. Lamping, R. D. Cannon, and B. C. Monk. 2005. Phosphorylation of Candida glabrata ATP-binding cassette transporter Cdr1p regulates drug efflux activity and ATPase stability. J. Biol. Chem. 280:94-103.
40. White, T. C., S. Holleman, F. Dy, L. F. Mirels, and D. A. Stevens. 2002. Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob. Agents Chemother. 46:1704-1713.
41. Winzeler, E. A., D. D. Shoemaker, A. Astromoff, H. Liang, K. Anderson, B. Andre, R. Bangham, R. Benito, J. D. Boeke, H. Bussey, A. M. Chu, C. Connelly, K. Davis, F. Dietrich, S. W. Dow, M. El Bakkoury, F. Foury, S. H. Friend, E. Gentalen, G. Giaever, J. H. Hegemann, T. Jones, M. Laub, H. Liao, N. Liebundguth, D. J. Lockhart, A. Lucau-Danila, M. Lussier, N. M'Rabet, P. Menard, M. Mittmann, C. Pai, C. Rebischung, J. L. Revuelta, L. Riles, C. J. Roberts, P. Ross-MacDonald, B. Scherens, M. Snyder, S. Sookhai-Mahadeo, R. K. Storms, S. Veronneau, M. Voet, G. Volckaert, T. R. Ward, R. Wysocki, G. S. Yen, K. Yu, K. Zimmermann, P. Philippsen, M. Johnston, and R. W. Davis. 1999. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285:901-906.
42. Wolfger, H., Y. M. Mamnun, and K. Kuchler. 2001. Fungal ABC proteins: pleiotropic drug resistance, stress response and cellular detoxification. Res. Microbiol. 152:375-389.
43. Yoshida, Y., and Y. Aoyama. 1987. Interaction of azole antifungal agents with cytochrome P-45014DM purified from Saccharomyces cerevisiae microsomes. Biochem. Pharmacol. 36:229-235.
44. Zhang, X., and W. S. Moye-Rowley. 2001. Saccharomyces cerevisiae multidrug resistance gene expression inversely correlates with the status of the F(0) component of the mitochondrial ATPase. J. Biol. Chem. 276:47844-47852.