A Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 11, 2009, Pages 4678-4685

  McManus, Brenda A ^a   Moran, Gary P ^a   Higgins, Judy A ^a   Sullivan, Derek J ^a   Coleman, David C ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; CYTOSINE DEAMINASE; FLUCYTOSINE; FLUOROURACIL; LEUCINE; PROTEIN FCA1P; SERINE; TETRACYCLINE; UNCLASSIFIED DRUG; URACIL PHOSPHORIBOSYLTRANSFERASE;

AMINO ACID SEQUENCE; ANTIFUNGAL RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; BROTH DILUTION; CANDIDA ALBICANS; CANDIDA DUBLINIENSIS; CONTROLLED STUDY; DEAMINATION; DNA SEQUENCE; FUNGAL GENE; FUNGAL STRAIN; FUNGUS ISOLATION; GENE EXPRESSION; GENE LOCUS; HOMOZYGOSITY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SUBSTITUTION REACTION;

AMINO ACID SUBSTITUTION; ANTIFUNGAL AGENTS; CANDIDA; CYTOSINE DEAMINASE; DRUG RESISTANCE, FUNGAL; FLUCYTOSINE; MICROBIAL SENSITIVITY TESTS; TETRACYCLINE;

EID: 70350329242     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00607-09     Document Type: Article

References (44)

1. Ahmad, S., Z. Khan, E. Mokaddas, and Z. U. Khan. 2004. Isolation and molecular identification of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Kuwait. J. Med. Microbiol. 53:633-637.
2. Al Mosaid, A., D. Sullivan, I. F. Salkin, D. Shanley, and D. C. Coleman. 2001. Differentiation of Candida dubliniensis from Candida albicans on Staib agar and caffeic acid-ferric citrate agar. J. Clin. Microbiol. 39:323-327.
3. Al Mosaid, A., D. J. Sullivan, and D. C. Coleman. 2003. Differentiation of Candida dubliniensis from Candida albicans on Pal's agar. J. Clin. Microbiol. 41:4787-4789.
4. Al Mosaid, A., D. J. Sullivan, I. Polacheck, F. A. Shaheen, O. Soliman, S. Al Hedaithy, S. Al Thawad, M. Kabadaya, and D. C. Coleman. 2005. Novel 5-flucytosine-resistant clade of Candida dubliniensis from Saudi Arabia and Egypt identified by Cd25 fingerprinting. J. Clin. Microbiol. 43:4026-4036.
5. Chapeland-Leclerc, F., J. Bouchoux, A. Goumar, C. Chastin, J. Villard, and T. Noel. 2005. Inactivation of the FCY2 gene encoding purine-cytosine permease promotes cross-resistance to flucytosine and fluconazole in Candida lusitaniae. Antimicrob. Agents Chemother. 49:3101-3108. (Pubitemid 41060546)
6. Clinical and Laboratory Standards Institute. 2002. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard; M27-A2. Clinical and Laboratory Standards Institute, Wayne, PA.
7. Dodgson, A. R., K. J. Dodgson, C. Pujol, M. A. Pfaller, and D. R. Soll. 2004. Clade-specific flucytosine resistance is due to a single nucleotide change in the FUR1 gene of Candida albicans. Antimicrob. Agents Chemother. 48:2223-2227.
8. Doern, G. V., T. A. Tubert, K. Chapin, and M. G. Rinaldi. 1986. Effect of medium composition on results of macrobroth dilution antifungal susceptibility testing of yeasts. J. Clin. Microbiol. 24:507-511.
9. Erbs, P., F. Exinger, and R. Jund. 1997. Characterization of the Saccharomyces cerevisiae FCY1 gene encoding cytosine deaminase and its homologue FCA1 of Candida albicans. Curr. Genet. 31:1-6. (Pubitemid 27077524)
10. Florent, M., T. Noel, G. Ruprich-Robert, B. Da Silva, V. Fitton-Ouhabi, C. Chastin, N. Papon, and F. Chapeland-Leclerc. 2009. Nonsense and missense mutations in FCY2 and FCY1 genes are responsible for flucytosine resistance and flucytosine-fluconazole cross-resistance in clinical isolates of Candida lusitaniae. Antimicrob. Agents Chemother. 53:2982-2990.
11. Gee, S. F., S. Joly, D. R. Soll, J. F. Meis, P. E. Verweij, I. Polacheck, D. J. Sullivan, and D. C. Coleman. 2002. Identification of four distinct genotypes of Candida dubliniensis and detection of microevolution in vitro and in vivo. J. Clin. Microbiol. 40:556-574.
12. Hanahan, D. 1983. Studies on transformation of Escherichia coli with plasmids. J. Mol. Biol. 166:557-580.
13. Hope, W. W., L. Tabernero, D. W. Denning, and M. J. Anderson. 2004. Molecular mechanisms of primary resistance to flucytosine in Candida albicans. Antimicrob. Agents Chemother. 48:4377-4386.
14. Hoskins, J., and J. S. Butler. 2008. RNA-based 5-fluorouracil toxicity requires the pseudouridylation activity of Cbf5p. Genetics 179:323-330.
15. Joly, S., C. Pujol, M. Rysz, K. Vargas, and D. R. Soll. 1999. Development and characterization of complex DNA fingerprinting probes for the infectious yeast Candida dubliniensis. J. Clin. Microbiol. 37:1035-1044. (Pubitemid 29140611)
16. Ko, T. P., J. J. Lin, C. Y. Hu, Y. H. Hsu, A. H. Wang, and S. H. Liaw. 2003. Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution. J. Biol. Chem. 278:19111-19117.
17. Kurtz, J. E., F. Exinger, P. Erbs, and R. Jund. 1999. New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism. Curr. Genet. 36:130-136.
18. McManus, B. A., D. C. Coleman, G. Moran, E. Pinjon, D. Diogo, M. E. Bougnoux, S. Borecka-Melkusova, H. Bujdakova, P. Murphy, C. d'Enfert, and D. J. Sullivan. 2008. Multilocus sequence typing reveals that the population structure of Candida dubliniensis is significantly less divergent than that of Candida albicans. J. Clin. Microbiol. 46:652-664.
19. McManus, B. A., D. J. Sullivan, G. P. Moran, C. D'Enfert, M. E. Bougnoux, M. A. Nunn, and D. C. Coleman. Genetic differences between avian and human isolates of Candida dubliniensis. Emerg. Infect. Dis. 15:1467-1470.
20. Moran, G., D. Sullivan, J. Morschhauser, and D. Coleman. 2002. The Candida dubliniensis CdCDR1 gene is not essential for fluconazole resistance. Antimicrob. Agents Chemother. 46:2829-2841.
21. Moran, G. P., D. Sanglard, S. M. Donnelly, D. B. Shanley, D. J. Sullivan, and D. C. Coleman. 1998. Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 42:1819-1830.
22. Noel, T., F. Francois, P. Paumard, C. Chastin, D. Brethes, and J. Villard. 2003. Flucytosine-fluconazole cross-resistance in purine-cytosine permease-deficient Candida lusitaniae clinical isolates: indirect evidence of a fluconazole uptake transporter. Antimicrob. Agents Chemother. 47:1275-1284.
23. Odds, F. C., M. E. Bougnoux, D. J. Shaw, J. M. Bain, A. D. Davidson, D. Diogo, M. D. Jacobsen, M. Lecomte, S. Y. Li, A. Tavanti, M. C. Maiden, N. A. Gow, and C. d'Enfert. 2007. Molecular phylogenetics of Candida albicans. Eukaryot. Cell 6:1041-1052.
24. Paluszynski, J. P., R. Klassen, and F. Meinhardt. 2008. Genetic prerequisites for additive or synergistic actions of 5-fluorocytosine and fluconazole in baker's yeast. Microbiology 154:3154-3164.
25. Paluszynski, J. P., R. Klassen, M. Rohe, and F. Meinhardt. 2006. Various cytosine/adenine permease homologues are involved in the toxicity of 5-fluorocytosine in Saccharomyces cerevisiae. Yeast 23:707-715.
26. Papon, N., T. Noel, M. Florent, S. Gibot-Leclerc, D. Jean, C. Chastin, J. Villard, and F. Chapeland-Leclerc. 2007. Molecular mechanism of flucytosine resistance in Candida lusitaniae: contribution of the FCY2, FCY1, and FUR1 genes to 5-fluorouracil and fluconazole cross-resistance. Antimicrob. Agents Chemother. 51:369-371.
27. Park, Y. N., and J. Morschhauser. 2005. Tetracycline-inducible gene expression and gene deletion in Candida albicans. Eukaryot. Cell 4:1328-1342.
28. Pfaffl, M. W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e45.
29. Pfaller, M. A., S. A. Messer, S. Gee, S. Joly, C. Pujol, D. J. Sullivan, D. C. Coleman, and D. R. Soll. 1999. In vitro susceptibilities of Candida dubliniensis isolates tested against the new triazole and echinocandin antifungal agents. J. Clin. Microbiol. 37:870-872.
30. Polacheck, I., J. Strahilevitz, D. Sullivan, S. Donnelly, I. F. Salkin, and D. C. Coleman. 2000. Recovery of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Israel. J. Clin. Microbiol. 38:170-174.
31. Polak, A., and H. J. Scholer. 1975. Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy 21:113-130.
32. Pujol, C., M. A. Pfaller, and D. R. Soll. 2004. Flucytosine resistance is restricted to a single genetic clade of Candida albicans. Antimicrob. Agents Chemother. 48:262-266.
33. Rodríguez-Tudela, J. L., F. Barchiesi, F. Bille, E. Chryssanthou, M. Cuenca-Estrella, D. Denning, J. P. Donnelly, B. Dupont, W. Fegeler, C. Moore, M. Richardson, and P. E. Verweij. 2003. Method for the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts. Clin. Microbiol. Infect. 9:i-viii.
34. T method. Nat. Protoc. 3:1101-1108.
35. Staib, P., G. P. Moran, D. J. Sullivan, D. C. Coleman, and J. Morschhauser. 2001. Isogenic strain construction and gene targeting in Candida dubliniensis. J. Bacteriol. 183:2859-2865.
36. Sullivan, D., K. Haynes, J. Bille, P. Boerlin, L. Rodero, S. Lloyd, M. Henman, and D. Coleman. 1997. Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals. J. Clin. Microbiol. 35:960-964.
37. Sullivan, D. J., G. P. Moran, and D. C. Coleman. 2005. Candida dubliniensis: ten years on. FEMS Microbiol. Lett. 253:9-17.
38. Sullivan, D. J., G. P. Moran, E. Pinjon, A. Al-Mosaid, C. Stokes, C. Vaughan, and D. C. Coleman. 2004. Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans. FEMS Yeast Res. 4:369-376.
39. Sullivan, D. J., T. J. Westerneng, K. A. Haynes, D. E. Bennett, and D. C. Coleman. 1995. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology 141:1507-1521.
40. Thompson, J. D., D. G. Higgins, and T. J. Gibson. 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.
41. Waldorf, A. R., and A. Polak. 1983. Mechanisms of action of 5-fluorocytosine. Antimicrob. Agents Chemother. 23:79-85.
42. Weber, E., C. Rodriguez, M. R. Chevallier, and R. Jund. 1990. The purine-cytosine permease gene of Saccharomyces cerevisiae: primary structure and deduced protein sequence of the FCY2 gene product. Mol. Microbiol. 4:585-596. (Pubitemid 20153123)
43. Whelan, W. L., and D. Kerridge. 1984. Decreased activity of UMP pyrophosphorylase associated with resistance to 5-fluorocytosine in Candida albicans. Antimicrob. Agents Chemother. 26:570-574.
44. Willis, A. M., W. A. Coulter, D. J. Sullivan, D. C. Coleman, J. R. Hayes, P. M. Bell, and P. J. Lamey. 2000. Isolation of C. dubliniensis from insulin-using diabetes mellitus patients. J. Oral Pathol. Med. 29:86-90.