ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in fluconazole-resistant Candida albicans clinical isolates

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 11, 2008, Pages 3851-3862

  Holmes, Ann R ^a   Lin, Ya Hsun ^a   Niimi, Kyoko ^a   Lamping, Erwin ^a   Keniya, Mikhail ^a   Niimi, Masakazu ^b   Tanabe, Koichi ^b   Monk, Brian C ^a   Cannon, Richard D ^a  

^a UNIVERSITY OF OTAGO   (New Zealand)

^b NATIONAL INSTITUTE OF INFECTIOUS DISEASES   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ABC TRANSPORTER; CDR1P PROTEIN; CDR2P PROTEIN; FLUCONAZOLE; FUNGUS ANTIBODY; POLYPEPTIDE; UNCLASSIFIED DRUG;

ANTIBIOTIC SENSITIVITY; ARTICLE; CANDIDA ALBICANS; CHEMOSENSITIZATION; CONTROLLED STUDY; FUNGAL STRAIN; FUNGUS ISOLATION; GENETIC CODE; GENETIC TRANSCRIPTION; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; STANDARDIZATION; WESTERN BLOTTING;

ANTIBODIES, FUNGAL; ANTIFUNGAL AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL TRANSPORT, ACTIVE; CANDIDA ALBICANS; CANDIDIASIS; DRUG RESISTANCE, FUNGAL; FLUCONAZOLE; FUNGAL PROTEINS; GENE EXPRESSION; GENES, FUNGAL; HUMANS; MEMBRANE TRANSPORT PROTEINS; RECOMBINANT PROTEINS; SACCHAROMYCES CEREVISIAE;

EID: 55849083537     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00463-08     Document Type: Article

References (58)

1. Calabrese, D., J. Bille, and D. Sanglard. 2000. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Microbiology 146:2743-2754.
2. Cannon, R. D., E. Lamping, A. R. Holmes, K. Niimi, K. Tanabe, M. Niimi, and B. C. Monk. 2007. Candida albicans drug resistance another way to cope with stress. Microbiology 153:3211-3217.
3. Chau, A. S., C. A. Mendrick, F. J. Sabatelli, D. Loebenberg, and P. M. McNicholas. 2004. Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob. Agents Chemother. 48:2124-2131.
4. Coste, A., A. Selmecki, A. Forche, D. Diogo, M. E. Bougnoux, C. d'Enfert, J. Berman, and D. Sanglard. 2007. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot. Cell 6:1889-1904.
5. Coste, A. T., M. Karababa, F. Ischer, J. Bille, and D. Sanglard. 2004. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot. Cell 3:1639-1652.
6. Cramer, J., S. Kopp, S. E. Bates, P. Chiba, and G. F. Ecker. 2007. Multi-specificity of drug transporters: probing inhibitor selectivity for the human drug efflux transporters ABCB1 and ABCG2. Chem. Med. Chem. 2:1783-1788.
7. Decottignies, A., M. Kolaczkowski, E. Balzi, and A. Goffeau. 1994. Solubilization and characterization of the overexpressed PDR5 multidrug resistance nucleotide triphosphatase of yeast. J. Biol. Chem. 269:12797-12803.
8. Frederiksen, P. D., S. Thiel, L. Jensen, A. G. Hansen, F. Matthiesen, and J. C. Jensenius. 2006. Quantification of mannan-binding lectin. J. Immunol. Methods 315:49-60.
9. Gaur, M., D. Choudhury, and R. Prasad. 2005. Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans. J. Mol. Microbiol. Biotechnol. 9:3-15.
10. Gauthier, C., S. Weber, A. M. Alarco, O. Alqawi, R. Daoud, E. Georges, and M. Raymond. 2003. Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters. Antimicrob. Agents Chemother. 47:1543-1554.
11. Goda, K., F. Fenyvesi, Z. Bacso, H. Nagy, T. Marian, A. Megyeri, Z. Krasznai, I. Juhasz, M. Vecsernyes, and G. Szabo, Jr. 2007. Complete inhibition of P-glycoprotein by simultaneous treatment with a distinct class of modulators and the UIC2 monoclonal antibody. J. Pharmacol. Exp. Ther. 320:81-88.
12. Heitman, J. 2005. Cell biology: a fungal Achilles' heel. Science 309:2175-2176.
13. Hiraga, K., S. Yamamoto, H. Fukuda, N. Hamanaka, and K. Oda. 2005. Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 328:1119-1125.
14. Holmes, A. R., S. Tsao, S. W. Ong, E. Lamping, K. Niimi, B. C. Monk, M. Niimi, A. Kaneko, B. R. Holland, J. Schmid, and R. D. Cannon. 2006. Heterozygosity and functional allelic variation in the Candida albicans efflux pump genes CDR1 and CDR2. Mol. Microbiol. 62:170-186.
15. Hooshdaran, M. Z., K. S. Barker, G. M. Hilliard, H. Kusch, J. Morschhauser, and P. D. Rogers. 2004. Proteomic analysis of azole resistance in Candida albicans clinical isolates. Antimicrob. Agents Chemother. 48:2733-2735.
16. Karababa, M., A. T. Coste, B. Rognon, J. Bille, and D. Sanglard. 2004. Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters. Antimicrob. Agents Chemother. 48:3064-3079.
17. Kusch, H., K. Biswas, S. Schwanfelder, S. Engelmann, P. D. Rogers, M. Hecker, and J. Morschhauser. 2004. A proteomic approach to understanding the development of multidrug-resistant Candida albicans strains. Mol. Genet. Genomics 271:554-565.
18. Laemmli, U. K., and S. F. Quittner. 1974. Maturation of the head of bacteriophage T4. IV. The proteins of the core of the tubular polyheads and in vitro cleavage of the head proteins. Virology 62:483-499.
19. Lamping, E., B. C. Monk, K. Niimi, A. R. Holmes, S. Tsao, K. Tanabe, M. Niimi, Y. Uehara, and R. D. Cannon. 2007. Characterization of three classes of membrane proteins involved in fungal azole resistance by functional hyperexpression in Saccharomyces cerevisiae. Eukaryot. Cell 6:1150-1165.
20. Lee, M. D., J. L. Galazzo, A. L. Staley, J. C. Lee, W. Warren, H. Fuernkranz, S. Chamberland, O. Lomovskaya, and G. H. Miller. 2001. Microbial fermentation-derived inhibitors of efflux-pump-mediated drug resistance. Il Farmaco. 56:81-85.
21. Liu, T. T., S. Znaidi, K. S. Barker, L. Xu, R. Homayouni, S. Saidane, J. Morschhauser, A. Nantel, M. Raymond, and P. D. Rogers. 2007. Genomewide expression and location analyses of the Candida albicans Tac1p regulon. Eukaryot. Cell 6:2122-2138.
22. Lopez-Ribot, J. L., R. K. McAtee, L. N. Lee, W. R. Kirkpatrick, T. C. White, D. Sanglard, and T. F. Patterson. 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.
23. Maebashi, K., M. Niimi, M. Kudoh, F. J. Fischer, K. Makimura, K. Niimi, R. J. Piper, K. Uchida, M. Arisawa, R. D. Cannon, and H. Yamaguchi. 2001. Mechanisms of fluconazole resistance in Candida albicans isolates from Japanese AIDS patients. J. Antimicrob. Chemother. 47:527-536.
24. Manoharlal, R., N. A. Gaur, S. L. Panwar, J. Morschhauser, and R. Prasad. 2008. Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans. Antimicrob. Agents Chemother. 52:1481-1492.
25. Marchetti, O., P. Moreillon, M. P. Glauser, J. Bille, and D. Sanglard. 2000. Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans. Antimicrob. Agents Chemother. 44:2373-2381.
26. Marr, K. A., C. N. Lyons, K. Ha, T. R. Rustad, and T. C. White. 2001. Inducible azole resistance associated with a heterogeneous phenotype in Candida albicans. Antimicrob. Agents Chemother. 45:52-59.
27. Monk, B. C., K. Niimi, S. Lin, A. Knight, T. B. Kardos, R. D. Cannon, A. King, D. Lun, and D. R. K. Harding. 2005. Surface-active fungicidal Dpeptide inhibitors of the plasma membrane proton pump that block azole resistance. Antimicrob. Agents Chemother. 49:57-70.
28. Morschhauser, J., K. S. Barker, T. T. Liu, J. Blass-Warmuth, R. Homayouni, and P. D. Rogers. 2007. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 3:e164.
29. Nakamura, K., M. Niimi, K. Niimi, A. R. Holmes, J. E. Yates, A. Decottignies, B. C. Monk, A. Goffeau, and R. D. Cannon. 2001. Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob. Agents Chemother. 45:3366-3374.
30. Niimi, K., D. R. Harding, R. Parshot, A. King, D. J. Lun, A. Decottignies, M. Niimi, S. Lin, R. D. Cannon, A. Goffeau, and B. C. Monk. 2004. Chemosensitization of fluconazole resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative. Antimicrob. Agents Chemother. 48:1256-1271.
31. Niimi, K., K. Maki, F. Ikeda, A. R. Holmes, E. Lamping, M. Niimi, B. C. Monk, and R. D. Cannon. 2006. Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob. Agents Chemother. 50:1148-1155.
32. Niimi, M., K. Niimi, Y. Takano, A. R. Holmes, F. J. Fischer, Y. Uehara, and R. D. Cannon. 2004. Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance. J. Antimicrob. Chemother. 54:999-1006.
33. Odds, F. C. 2003. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 52:1.
34. Park, S., and D. S. Perlin. 2005. Establishing surrogate markers for fluconazole resistance in Candida albicans. Microb. Drug Resist. 11:232-238.
35. 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.
36. Pina-Vaz, C., A. G. Rodrigues, S. Costa-de-Oliveira, E. Ricardo, and P. A. Mardh. 2005. Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry. J. Antimicrob. Chemother. 56:678-685.
37. Ribeiro, M. A., C. R. Paula, R. John, J. R. Perfect, and G. M. Cox. 2005. Phenotypic and genotypic evaluation of fluconazole resistance in vaginal Candida strains isolated from HIV-infected women from Brazil. Med. Mycol. 43:647-650.
38. Rogers, P. D., and K. S. Barker. 2003. Genome-wide expression profile analysis reveals coordinately regulated genes associated with stepwise acquisition of azole resistance in Candida albicans clinical isolates. Antimicrob. Agents Chemother. 47:1220-1227.
39. Rustad, T. R., D. A. Stevens, M. A. Pfaller, and T. C. White. 2002. Homozygosity at the Candida albicans MTL locus associated with azole resistance. Microbiology 148:1061-1072.
40. Sanglard, D., and J. Bille. 2002. Current understanding of the modes of action of and resistance mechanisms to conventional and emerging antifungal agents for treatment of Candida infections, p. 349-383. In R. Calderone (ed.), Candida and candidiasis. ASM Press, Washington, DC.
41. Sanglard, D., F. Ischer, M. Monod, and J. Bille. 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.
42. Schuetzer-Muehlbauer, M., B. Willinger, R. Egner, G. Ecker, and K. Kuchler. 2003. Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast. Int. J. Antimicrob. Agents 22:291-300.
43. Shen, H., M. M. An, J. Wang de, Z. Xu, J. D. Zhang, P. H. Gao, Y. Y. Cao, Y. B. Cao, and Y. Y. Jiang. 2007. Fcr1p inhibits development of fluconazole resistance in Candida albicans by abolishing CDR1 induction. Biol. Pharm. Bull. 30:68-73.
44. Shukla, S., Z. E. Sauna, R. Prasad, and S. V. Ambudkar. 2004. Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans. Biochem. Biophys. Res. Commun. 322:520-525.
45. Sipos, G., and K. Kuchler. 2006. Fungal ATP-binding cassette (ABC) transporters in drug resistance and detoxification. Curr. Drug Targets 7:471-481.
46. Steinbach, W. J., J. L. Reedy, R. A. Cramer, Jr., J. R. Perfect, and J. Heitman. 2007. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat. Rev. Microbiol. 5:418-430.
47. Sun, S., Y. Li, Q. Guo, C. Shi, J. Yu, and L. Ma. 2008. In vitro interactions between tacrolimus and azoles against Candida albicans determined by different methods. Antimicrob. Agents Chemother. 52:409-417.
48. Tanabe, K., E. Lamping, K. Adachi, Y. Takano, K. Kawabata, Y. Shizuri, M. Niimi, and Y. Uehara. 2007. Inhibition of fungal ABC transporters by unnarmicin A and unnarmicin C, novel cyclic peptides from marine bacterium. Biochem. Biophys. Res. Commun. 364:990-995.
49. Uppuluri, P., J. Nett, J. Heitman, and D. Andes. 2008. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob. Agents Chemother. 52:1127-1132.
50. Warren, C. A., L. Mok, S. Gordon, A. F. Fouad, and M. S. Gold. 2008. Quantification of neural protein in extirpated tooth pulp. J. Endod. 34:7-10.
51. Watkins, W. J., L. Chong, A. Cho, R. Hilgenkamp, M. Ludwikow, N. Garizi, N. Iqbal, J. Barnard, R. Singh, D. Madsen, K. Lolans, O. Lomovskaya, U. Oza, P. Kumaraswamy, A. Blecken, S. Bai, D. J. Loury, D. C. Griffith, and M. N. Dudley. 2007. Quinazolinone fungal efflux pump inhibitors. Part 3. (N-Methyl)piperazine variants and pharmacokinetic optimization. Bioorg. Med. Chem. Lett. 17:2802-2806.
52. White, T. C. 1997. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob. Agents Chemother. 41:1482-1487.
53. 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.
54. Xu, D., B. Jiang, T. Ketela, S. Lemieux, K. Veillette, N. Martel, J. Davison, S. Sillaots, S. Trosok, C. Bachewich, H. Bussey, P. Youngman, and T. Roemer. 2007. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. PLoS Pathog. 3:e92.
55. Xu, Z., L. X. Zhang, J. D. Zhang, Y. B. Cao, Y. Y. Yu, D. J. Wang, K. Ying, W. S. Chen, and Y. Y. Jiang. 2006. cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients. Int. J. Med. Microbiol. 296:421-434.
56. Yamamoto, S., K. Hiraga, A. Abiko, N. Hamanaka, and K. Oda. 2005. A new function of isonitrile as an inhibitor of the Pdr5p multidrug ABC transporter in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 330:622-628.
57. Yan, L., J. D. Zhang, Y. B. Cao, P. H. Gao, and Y. Y. Jiang. 2007. Proteomic analysis reveals a metabolism shift in a laboratory fluconazole-resistant Candida albicans strain. J. Proteome. Res. 6:2248-2256.
58. Yasar, U., G. Tybring, M. Hidestrand, M. Oscarson, M. Ingelman-Sundberg, M. L. Dahl, and E. Eliasson. 2001. Role of CYP2C9 polymorphism in losartan oxidation. Drug Metab. Dispos. 29:1051-1056.