Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata

Pharmaceuticals

Volumn 4, Issue 1, 2011, Pages 169-186

  Tscherner, Michael ^a   Schwarzmüller, Tobias ^a   Kuchler, Karl ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Candida glabrata; Drug resistance; Fungal pathogenesis; Virulence

Indexed keywords

AMPHOTERICIN B; ANTIFUNGAL AGENT; ECHINOCANDIN; POLYENE; PROTEIN ACE2; PYRROLE DERIVATIVE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ANTIFUNGAL ACTIVITY; ANTIFUNGAL RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; CANDIDA GLABRATA; CANDIDIASIS; CELL ADHESION; CHROMOSOME ABERRATION; DISEASE MODEL; DRUG EFFICACY; DRUG TARGETING; FUNGAL MORPHOLOGY; FUNGAL VIRULENCE; FUNGICIDAL ACTIVITY; GENE MUTATION; GENOME ANALYSIS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE RESPONSE; IMMUNOSURVEILLANCE; MOLECULAR DYNAMICS; MYCOSIS; NEPHROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PHAGOLYSOSOME; PHENOTYPIC VARIATION; PIGMENTATION; PROTEIN ANALYSIS; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL; TANDEM REPEAT; TRANSCRIPTION REGULATION;

EID: 79551609119     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph4010169     Document Type: Review

References (121)

1. Pfaller, M.A.; Diekema, D.J. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 2007, 20, 133-163.
2. Nace, H.L.; Horn, D.; Neofytos, D. Epidemiology and outcome of multiple-species candidemia at a tertiary care center between 2004 and 2007. Diagn. Microbiol. Infect. Dis. 2009, 64, 289-294.
3. Pfaller, M.A.; Boyken, L.; Hollis, R.J.; Kroeger, J.; Messer, S.A.; Tendolkar, S.; Diekema, D.J. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J. Clin. Microbiol. 2008, 46, 150-156.
4. Tortorano, A.M.; Kibbler, C.; Peman, J.; Bernhardt, H.; Klingspor, L.; Grillot, R. Candidaemia in Europe: epidemiology and resistance. Int. J. Antimicrob. Agents 2006, 27, 359-366.
5. Wilson, D.; Thewes, S.; Zakikhany, K.; Fradin, C.; Albrecht, A.; Almeida, R.; Brunke, S.; Grosse, K.; Martin, R.; Mayer, F.; Leonhardt, I.; Schild, L.; Seider, K.; Skibbe, M.; Slesiona, S.; Waechtler, B.; Jacobsen, I.; Hube, B. Identifying infection-associated genes of Candida albicans in the postgenomic era. FEMS Yeast Res. 2009, 9, 688-700.
6. Brown, A.J.; Odds, F.C.; Gow, N.A. Infection-related gene expression in Candida albicans. Curr. Opin. Microbiol. 2007, 10, 307-313.
7. Cannon, R.D.; Lamping, E.; Holmes, A.R.; Niimi, K.; Tanabe, K.; Niimi, M.; Monk, B.C. Candida albicans drug resistance another way to cope with stress. Microbiology 2007, 153, 3211-3217.
8. Biswas, S.; Van Dijck, P.; Datta, A. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol. Mol. Biol. Rev. 2007, 71, 348-376.
9. Kumamoto, C.A.; Vinces, M.D. Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell. Microbiol. 2005, 7, 1546-1554.
10. Schaller, M.; Borelli, C.; Korting, H.C.; Hube, B. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 2005, 48, 365-377.
11. De Las Penas, A.; Pan, S.J.; Castano, I.; Alder, J.; Cregg, R.; Cormack, B.P. Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev. 2003, 17, 2245-2258.
12. Castano, I.; Pan, S.J.; Zupancic, M.; Hennequin, C.; Dujon, B.; Cormack, B.P. Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol. Microbiol. 2005, 55, 1246-1258.
13. Iraqui, I.; Garcia-Sanchez, S.; Aubert, S.; Dromer, F.; Ghigo, J.M.; d'Enfert, C.; Janbon, G. The Yak1p kinase controls expression of adhesins and biofilm formation in Candida glabrata in a Sir4p-dependent pathway. Mol. Microbiol. 2005, 55, 1259-1271.
14. Mundy, R.D.; Cormack, B. Expression of Candida glabrata Adhesins after Exposure to Chemical Preservatives. J. Infect. Dis. 2009, 199, 1891-1898.
15. Domergue, R.; Castano, I.; De Las Penas, A.; Zupancic, M.; Lockatell, V.; Hebel, J.R.; Johnson, D.; Cormack, B.P. Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science 2005, 308, 866-870.
16. Kaur, R.; Ma, B.; Cormack, B.P. A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata. Proc. Natl. Acad. Sci. USA 2007, 104, 7628-7633.
17. Kamran, M.; Calcagno, A.M.; Findon, H.; Bignell, E.; Jones, M.D.; Warn, P.; Hopkins, P.; Denning, D.W.; Butler, G.; Rogers, T.; Muhlschlegel, F.A.; Haynes, K. Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence. Eukaryot. Cell 2004, 3, 546-552.
18. Stead, D.; Findon, H.; Yin, Z.; Walker, J.; Selway, L.; Cash, P.; Dujon, B.A.; Hennequin, C.; Brown, A.J.; Haynes, K. Proteomic changes associated with inactivation of the C. glabrata ACE2 virulence-moderating gene. Proteomics 2005, 5, 1838-1848.
19. Stead, D.A.; Walker, J.; Holcombe, L.; Gibbs, S.R.; Yin, Z.; Selway, L.; Butler, G.; Brown, A.J.; Haynes, K. Impact of the transcriptional regulator, Ace2, on the Candida glabrata secretome. Proteomics 2009, 10, 212-223.
20. MacCallum, D.M.; Findon, H.; Kenny, C.C.; Butler, G.; Haynes, K.; Odds, F.C. Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts. Infect. Immun. 2006, 74, 5244-5248.
21. Brunke, S.; Seider, K.; Almeida, R.S.; Heyken, A.; Fleck, C.B.; Brock, M.; Barz, D.; Rupp, S.; Hube, B. Candida glabrata tryptophan-based pigment production via the Ehrlich pathway. Mol. Microbiol. 2010, 76, 25-47.
22. Roetzer, A.; Gratz, N.; Kovarik, P.; Schüller, C. Autophagy supports Candida glabrata survival during phagocytosis. Cell. Microbiol. 2010, 12, 199-216.
23. Cuellar-Cruz, M.; Briones-Martin-del-Campo, M.; Canas-Villamar, I.; Montalvo-Arredondo, J.; Riego-Ruiz, L.; Castano, I.; De Las Penas, A. High resistance to oxidative stress in the fungal pathogen Candida glabrata is mediated by a single catalase, Cta1p, and is controlled by the transcription factors Yap1p, Skn7p, Msn2p, and Msn4p. Eukaryot. Cell 2008, 7, 814-825.
24. Ferrari, S.; Ischer, F.; Calabrese, D.; Posteraro, B.; Sanguinetti, M.; Fadda, G.; Rohde, B.; Bauser, C.; Bader, O.; Sanglard, D. Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog. 2009, 5, e1000268.
25. Torelli, R.; Posteraro, B.; Ferrari, S.; La Sorda, M.; Fadda, G.; Sanglard, D.; Sanguinetti, M. The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1- dependent azole resistance of Candida glabrata. Mol. Microbiol. 2008, 68, 186-201.
26. Sanglard, D.; Ischer, F.; Bille, J. Role of ATP-binding-cassette transporter genes in highfrequency acquisition of resistance to azole antifungals in Candida glabrata. Antimicrob. Agents Chemother. 2001, 45, 1174-1183.
27. Katiyar, S.; Pfaller, M.; Edlind, T. Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob. Agents Chemother. 2006, 50, 2892-2894.
28. Thompson, G.R., 3rd; Wiederhold, N.P.; Vallor, A.C.; Villareal, N.C.; Lewis, J.S., 2nd; Patterson, T.F. Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob. Agents Chemother. 2008, 52, 3783-3785.
29. Cleary, J.D.; Garcia-Effron, G.; Chapman, S.W.; Perlin, D.S. Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment. Antimicrob. Agents Chemother. 2008, 52, 2263-2265.
30. Garcia-Effron, G.; Lee, S.; Park, S.; Cleary, J.D.; Perlin, D.S. Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-β-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob. Agents Chemother. 2009, 53, 3690-3699.
31. Sundstrom, P. Adhesins in Candida albicans. Curr. Opin. Microbiol. 1999, 2, 353-357.
32. Hoyer, L.L. The ALS gene family of C. albicans. Trends Microbiol. 2001, 9, 176-180.
33. Weig, M.; Jansch, L.; Gross, U.; De Koster, C.G.; Klis, F.M.; De Groot, P.W. Systematic identification in silico of covalently bound cell wall proteins and analysis of protein-polysaccharide linkages of the human pathogen Candida glabrata. Microbiology 2004, 150, 3129-3144.
34. Kaur, R.; Domergue, R.; Zupancic, M.L.; Cormack, B.P. A yeast by any other name: C. glabrata and its interaction with the host. Curr. Opin. Microbiol. 2005, 8, 378-384.
35. Thierry, A.; Bouchier, C.; Dujon, B.; Richard, G.F. Megasatellites: a peculiar class of giant minisatellites in genes involved in cell adhesion and pathogenicity in Candida glabrata. Nucleic. Acids Res. 2008, 36, 5970-5982.
36. Zupancic, M.L.; Frieman, M.; Smith, D.; Alvarez, R.A.; Cummings, R.D.; Cormack, B.P. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol. Microbiol. 2008, 68, 547-559.
37. de Groot, P.W.; Kraneveld, E.A.; Yin, Q.Y.; Dekker, H.L.; Gross, U.; Crielaard, W.; de Koster, C.G.; Bader, O.; Klis, F.M.; Weig, M. The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins. Eukaryot. Cell 2008, 7, 1951-1964.
38. Rusche, L.N.; Kirchmaier, A.L.; Rine, J. The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu. Rev. Biochem. 2003, 72, 481-516.
39. Ma, B.; Pan, S.J.; Domergue, R.; Rigby, T.; Whiteway, M.; Johnson, D.; Cormack, B.P. Highaffinity transporters for NAD+ precursors in C. glabrata are regulated by Hst1 and induced in response to niacin limitation. Mol. Cell. Biol. 2009, 29, 4067-4079.
40. Ma, B.; Pan, S.J.; Zupancic, M.L.; Cormack, B.P. Assimilation of NAD(+) precursors in Candida glabrata. Mol. Microbiol. 2007, 66, 14-25.
41. Krysan, D.J.; Ting, E.L.; Abeijon, C.; Kroos, L.; Fuller, R.S. Yapsins are a family of aspartyl proteases required for cell wall integrity in Saccharomyces cerevisiae. Eukaryot. Cell 2005, 4, 1364-1374.
42. Albrecht, A.; Felk, A.; Pichova, I.; Naglik, J.R.; Schaller, M.; de Groot, P.; Maccallum, D.; Odds, F.C.; Schafer, W.; Klis, F.; Monod, M.; Hube, B. Glycosylphosphatidylinositol-anchored proteases of C. albicans target proteins necessary for both cellular processes and host-pathogen interactions. J. Biol. Chem. 2006, 281, 688-694.
43. Nelson, B.; Kurischko, C.; Horecka, J.; Mody, M.; Nair, P.; Pratt, L.; Zougman, A.; McBroom, L.D.; Hughes, T.R.; Boone, C.; Luca, F.C. RAM: a conserved signaling network that regulates Ace2p transcriptional activity and polarized morphogenesis. Mol. Biol. Cell 2003, 14, 3782-3803.
44. Colman-Lerner, A.; Chin, T.E.; Brent, R. Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 2001, 107, 739-750.
45. O'Conallain, C.; Doolin, M.T.; Taggart, C.; Thornton, F.; Butler, G. Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae. Mol. Gen. Genet. 1999, 262, 275-282.
46. King, L.; Butler, G. Ace2p, a regulator of CTS1 (chitinase) expression, affects pseudohyphal production in S. cerevisiae. Curr. Genet. 1998, 34, 183-191.
47. Jacobsen, I.D.; Brunke, S.; Seider, K.; Schwarzmuller, T.; Firon, A.; d'Enfert, C.; Kuchler, K.; Hube, B. C. Glabrata persistence in mice does not depend on host immunosuppression and is unaffected by fungal amino acid auxotrophy. Infect. Immun. 2010, 78, 1066-1077.
48. Calcagno, A.M.; Bignell, E.; Warn, P.; Jones, M.D.; Denning, D.W.; Muhlschlegel, F.A.; Rogers, T.R.; Haynes, K. C. Glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation. Mol. Microbiol. 2003, 50, 1309-1318.
49. Roetzer, A.; Gregori, C.; Jennings, A.M.; Quintin, J.; Ferrandon, D.; Butler, G.; Kuchler, K.; Ammerer, G.; Schüller, C. C. Glabrata environmental stress response involves S. cerevisiae Msn2/4 orthologous transcription factors. Mol. Microbiol. 2008, 69, 603-620.
50. Brennan, M.; Thomas, D.Y.; Whiteway, M.; Kavanagh, K. Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae. FEMS Immunol. Med. Microbiol. 2002, 34, 153-157.
51. Mylonakis, E.; Moreno, R.; El Khoury, J.B.; Idnurm, A.; Heitman, J.; Calderwood, S.B.; Ausubel, F.M.; Diener, A. Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect. Immun. 2005, 73, 3842-3850.
52. Fuchs, B.B.; Eby, J.; Nobile, C.J.; El Khoury, J.B.; Mitchell, A.P.; Mylonakis, E. Role of filamentation in Galleria mellonella killing by C. albicans. Microbes Infect. 2010, 12, 488-496.
53. Pukkila-Worley, R.; Peleg, A.Y.; Tampakakis, E.; Mylonakis, E. Candida albicans hyphal formation and virulence assessed using a Caenorhabditis elegans infection model. Eukaryot. Cell 2009, 8, 1750-1758.
54. Okoli, I.; Coleman, J.J.; Tempakakis, E.; An, W.F.; Holson, E.; Wagner, F.; Conery, A.L.; Larkins-Ford, J.; Wu, G.; Stern, A.; Ausubel, F.M.; Mylonakis, E. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay. PLoS One 2009, 4, e7025.
55. Nosanchuk, J.D.; Gomez, B.L.; Youngchim, S.; Diez, S.; Aisen, P.; Zancope-Oliveira, R.M.; Restrepo, A.; Casadevall, A.; Hamilton, A.J. Histoplasma capsulatum synthesizes melanin-like pigments in vitro and during mammalian infection. Infect. Immun. 2002, 70, 5124-5131.
56. Jahn, B.; Koch, A.; Schmidt, A.; Wanner, G.; Gehringer, H.; Bhakdi, S.; Brakhage, A.A. Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect. Immun. 1997, 65, 5110-5117.
57. Kwon-Chung, K.J.; Tom, W.K.; Costa, J.L. Utilization of indole compounds by C. neoformans to produce a melanin-like pigment. J. Clin. Microbiol. 1983, 18, 1419-1421.
58. Jacobson, E.S.; Tinnell, S.B. Antioxidant function of fungal melanin. J. Bacteriol. 1993, 175, 7102-7104.
59. Jacobson, E.S. Pathogenic roles for fungal melanins. Clin. Microbiol. Rev. 2000, 13, 708-717.
60. Morgenstern, D.E.; Gifford, M.A.; Li, L.L.; Doerschuk, C.M.; Dinauer, M.C. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J. Exp. Med. 1997, 185, 207-218.
61. Mayser, P.; Wenzel, M.; Kramer, H.J.; Kindler, B.L.; Spiteller, P.; Haase, G. Production of indole pigments by Candida glabrata. Med. Mycol. 2007, 45, 519-524.
62. Hazelwood, L.A.; Tai, S.L.; Boer, V.M.; de Winde, J.H.; Pronk, J.T.; Daran, J.M. A new physiological role for Pdr12p in S. cerevisiae: export of aromatic and branched-chain organic acids produced in amino acid catabolism. FEMS Yeast Res. 2006, 6, 937-945.
63. Polakova, S.; Blume, C.; Zarate, J.A.; Mentel, M.; Jorck-Ramberg, D.; Stenderup, J.; Piskur, J. Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata. Proc. Natl. Acad. Sci. USA 2009, 106, 2688-2693.
64. Verstrepen, K.J.; Fink, G.R. Genetic and epigenetic mechanisms underlying cell-surface variability in protozoa and fungi. Annu. Rev. Genet. 2009, 43, 1-24.
65. Levdansky, E.; Romano, J.; Shadkchan, Y.; Sharon, H.; Verstrepen, K.J.; Fink, G.R.; Osherov, N. Coding tandem repeats generate diversity in Aspergillus fumigatus genes. Eukaryot. Cell 2007, 6, 1380-1391.
66. Lachke, S.A.; Srikantha, T.; Tsai, L.K.; Daniels, K.; Soll, D.R. Phenotypic switching in Candida glabrata involves phase-specific regulation of the metallothionein gene MT-II and the newly discovered hemolysin gene HLP. Infect. Immun. 2000, 68, 884-895.
67. Lachke, S.A.; Joly, S.; Daniels, K.; Soll, D.R. Phenotypic switching and filamentation in Candida glabrata. Microbiology 2002, 148, 2661-2674.
68. Brockert, P.J.; Lachke, S.A.; Srikantha, T.; Pujol, C.; Galask, R.; Soll, D.R. Phenotypic switching and mating type switching of Candida glabrata at sites of colonization. Infect. Immun. 2003, 71, 7109-7118.
69. Srikantha, T.; Daniels, K.J.; Wu, W.; Lockhart, S.R.; Yi, S.; Sahni, N.; Ma, N.; Soll, D.R. Dark brown is the more virulent of the switch phenotypes of Candida glabrata. Microbiology 2008, 154, 3309-3318.
70. Nicola, A.M.; Casadevall, A.; Goldman, D.L. Fungal killing by mammalian phagocytic cells. Curr. Opin. Microbiol. 2008, 11, 313-317.
71. Alvarez, M.; Casadevall, A. Phagosome extrusion and host-cell survival after C. neoformans phagocytosis by macrophages. Curr. Biol. 2006, 16, 2161-2165.
72. Ma, H.; Croudace, J.E.; Lammas, D.A.; May, R.C. Expulsion of live pathogenic yeast by macrophages. Curr. Biol. 2006, 16, 2156-2160.
73. Geisow, M.J.; D'Arcy Hart, P.; Young, M.R. Temporal changes of lysosome and phagosome Ph during phagolysosome formation in macrophages: studies by fluorescence spectroscopy. J. Cell. Biol. 1981, 89, 645-652.
74. Levitz, S.M.; Nong, S.H.; Seetoo, K.F.; Harrison, T.S.; Speizer, R.A.; Simons, E.R. Cryptococcus neoformans resides in an acidic phagolysosome of human macrophages. Infect. Immun. 1999, 67, 885-890.
75. Chaves, G.M.; Bates, S.; Maccallum, D.M.; Odds, F.C. C. Albicans GRX2, encoding a putative glutaredoxin, is required for virulence in a murine model. Genet. Mol. Res. 2007, 6, 1051-1063.
76. Missall, T.A.; Pusateri, M.E.; Lodge, J.K. Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans. Mol. Microbiol. 2004, 51, 1447-1458.
77. Frohner, I.E.; Bourgeois, C.; Yatsyk, K.; Majer, O.; Kuchler, K. Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol. Microbiol. 2009, 71, 240-252.
78. Paris, S.; Wysong, D.; Debeaupuis, J.P.; Shibuya, K.; Philippe, B.; Diamond, R.D.; Latge, J.P. Catalases of Aspergillus fumigatus. Infect. Immun. 2003, 71, 3551-3562.
79. Goffeau, A. Drug resistance: the fight against fungi. Nature 2008, 452, 541-542.
80. Cowen, L.E.; Steinbach, W.J. Stress, drugs, and evolution: the role of cellular signaling in fungal drug resistance. Eukaryot. Cell 2008, 7, 747-764.
81. Odds, F.C.; Brown, A.J.; Gow, N.A. Antifungal agents: mechanisms of action. Trends Microbiol. 2003, 11, 272-279.
82. Vanden Bossche, H.; Koymans, L.; Moereels, H. P450 inhibitors of use in medical treatment: focus on mechanisms of action. Pharmacol. Ther. 1995, 67, 79-100.
83. Lopez-Ribot, J.L.; McAtee, R.K.; Lee, L.N.; Kirkpatrick, W.R.; White, T.C.; Sanglard, D.; Patterson, T.F. Distinct patterns of gene expression associated with development of fluconazole resistance in serial C. albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob. Agents Chemother. 1998, 42, 2932-2937.
84. Perea, S.; Lopez-Ribot, J.L.; Kirkpatrick, W.R.; McAtee, R.K.; Santillan, R.A.; Martinez, M.; Calabrese, D.; Sanglard, D.; Patterson, T.F. 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. 2001, 45, 2676-2684.
85. Henry, K.W.; Nickels, J.T.; Edlind, T.D. Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob. Agents Chemother. 2000, 44, 2693-2700.
86. Vermitsky, J.P.; Edlind, T.D. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob. Agents Chemother. 2004, 48, 3773-3781.
87. Sanguinetti, M.; Posteraro, B.; Fiori, B.; Ranno, S.; Torelli, R.; Fadda, G. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob. Agents Chemother. 2005, 49, 668-679.
88. Sanglard, D.; Kuchler, K.; Ischer, F.; Pagani, J.L.; Monod, M.; Bille, J. Mechanisms of resistance to azole antifungal agents in C. albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob. Agents Chemother. 1995, 39, 2378-2386.
89. Sanglard, D.; Ischer, F.; Calabrese, D.; Majcherczyk, P.A.; Bille, J. The ATP binding cassette transporter gene CgCDR1 from C. glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob. Agents Chemother. 1999, 43, 2753-2765.
90. Sanglard, D.; Ischer, F.; Monod, M.; Bille, J. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 1997, 143, 405-416.
91. White, T.C. 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. 1997, 41, 1482-1487.
92. Bennett, J.E.; Izumikawa, K.; Marr, K.A. Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob. Agents Chemother. 2004, 48, 1773-1777.
93. Miyazaki, H.; Miyazaki, Y.; Geber, A.; Parkinson, T.; Hitchcock, C.; Falconer, D.J.; Ward, D.J.; Marsden, K.; Bennett, J.E. Fluconazole resistance associated with drug efflux and increased transcription of a drug transporter gene, PDH1, in Candida glabrata. Antimicrob. Agents Chemother. 1998, 42, 1695-1701.
94. Sipos, G.; Kuchler, K. Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr. Drug Targets 2006, 7, 471-481.
95. Nakayama, H.; Izuta, M.; Nakayama, N.; Arisawa, M.; Aoki, Y. Depletion of the squalene synthase (ERG9) gene does not impair growth of Candida glabrata in mice. Antimicrob. Agents Chemother. 2000, 44, 2411-2418.
96. Nakayama, H.; Tanabe, K.; Bard, M.; Hodgson, W.; Wu, S.; Takemori, D.; Aoyama, T.; Kumaraswami, N.S.; Metzler, L.; Takano, Y.; Chibana, H.; Niimi, M. The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum. J. Antimicrob. Chemother. 2007, 60, 1264-1272.
97. Ellis, D. Amphotericin B: spectrum and resistance. J. Antimicrob. Chemother. 2002, 49 (Suppl 1), 7-10.
98. Sterling, T.R.; Merz, W.G. Resistance to amphotericin B: emerging clinical and microbiological patterns. Drug Resist. Updat. 1998, 1, 161-165.
99. Nolte, F.S.; Parkinson, T.; Falconer, D.J.; Dix, S.; Williams, J.; Gilmore, C.; Geller, R.; Wingard, J.R. Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob. Agents Chemother. 1997, 41, 196-199.
100. Douglas, C.M. Fungal beta(1,3)-D-glucan synthesis. Med. Mycol. 2001, 39 (Suppl 1), 55-66.
101. Perlin, D.S. Resistance to echinocandin-class antifungal drugs. Drug Resist. Updat. 2007, 10, 121-130.
102. Schuetzer-Muehlbauer, M.; Willinger, B.; Krapf, G.; Enzinger, S.; Presterl, E.; Kuchler, K. The Candida albicans Cdr2p ATP-binding cassette (ABC) transporter confers resistance to caspofungin. Mol. Microbiol. 2003, 48, 225-235.
103. Gulshan, K.; Moye-Rowley, W.S. Multidrug resistance in fungi. Eukaryot. Cell 2007, 6, 1933-1942.
104. Li, X.Z.; Nikaido, H. Efflux-mediated drug resistance in bacteria. Drugs 2004, 64, 159-204.
105. Szakacs, G.; Paterson, J.K.; Ludwig, J.A.; Booth-Genthe, C.; Gottesman, M.M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 2006, 5, 219-234.
106. Jones, P.M.; George, A.M. Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling. Int. J. Parasitol. 2005, 35, 555-566.
107. Thakur, J.K.; Arthanari, H.; Yang, F.; Pan, S.J.; Fan, X.; Breger, J.; Frueh, D.P.; Gulshan, K.; Li, D.K.; Mylonakis, E.; Struhl, K.; Moye-Rowley, W.S.; Cormack, B.P.; Wagner, G.; Naar, A.M. A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature 2008, 452, 604-609.
108. Bouchara, J.P.; Zouhair, R.; Le Boudouil, S.; Renier, G.; Filmon, R.; Chabasse, D.; Hallet, J.N.; Defontaine, A. In vivo selection of an azole-resistant petite mutant of Candida glabrata. J. Med. Microbiol. 2000, 49, 977-984.
109. Tsai, H.F.; Krol, A.A.; Sarti, K.E.; Bennett, J.E. Candida glabrata PDR1, a transcriptional regulator of a pleiotropic drug resistance network, mediates azole resistance in clinical isolates and petite mutants. Antimicrob. Agents Chemother. 2006, 50, 1384-1392.
110. Hallstrom, T.C.; Moye-Rowley, W.S. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. J. Biol. Chem. 2000, 275, 37347-37356.
111. Borecka-Melkusova, S.; Kozovska, Z.; Hikkel, I.; Dzugasova, V.; Subik, J. RPD3 and ROM2 are required for multidrug resistance in Saccharomyces cerevisiae. FEMS Yeast Res. 2008, 8, 414-424.
112. Smith, W.L.; Edlind, T.D. Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals: correlation with reduction in CDR and ERG upregulation. Antimicrob. Agents Chemother. 2002, 46, 3532-3539.
113. Wurtele, H.; Tsao, S.; Lepine, G.; Mullick, A.; Tremblay, J.; Drogaris, P.; Lee, E.H.; Thibault, P.; Verreault, A.; Raymond, M. Modulation of histone H3 lysine 56 acetylation as an antifungal therapeutic strategy. Nat. Med. 2010, 16, 774-780.
114. Scherens, B.; Goffeau, A. The uses of genome-wide yeast mutant collections. Genome Biol. 2004, 5, 229.
115. Jones, G.M.; Stalker, J.; Humphray, S.; West, A.; Cox, T.; Rogers, J.; Dunham, I.; Prelich, G. A systematic library for comprehensive overexpression screens in Saccharomyces cerevisiae. Nat. Methods 2008, 5, 239-241.
116. Kumar, A.; Cheung, K.H.; Ross-Macdonald, P.; Coelho, P.S.; Miller, P.; Snyder, M. TRIPLES: a database of gene function in Saccharomyces cerevisiae. Nucleic Acids Res 2000, 28, 81-84.
117. Liu, O.W.; Chun, C.D.; Chow, E.D.; Chen, C.; Madhani, H.D.; Noble, S.M. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 2008, 135, 174-188.
118. Homann, O.R.; Dea, J.; Noble, S.M.; Johnson, A.D. A phenotypic profile of the Candida albicans regulatory network. PLoS Genet. 2009, 5, e1000783.
119. Nagalakshmi, U.; Wang, Z.; Waern, K.; Shou, C.; Raha, D.; Gerstein, M.; Snyder, M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 2008, 320, 1344-1349.
120. Hegedus, Z.; Zakrzewska, A.; Agoston, V.C.; Ordas, A.; Racz, P.; Mink, M.; Spaink, H.P.; Meijer, A.H. Deep sequencing of the zebrafish transcriptome response to mycobacterium infection. Mol. Immunol. 2009, 46, 2918-2930.
121. Costanzo, M.; Baryshnikova, A.; Bellay, J.; Kim, Y.; Spear, E.D.; Sevier, C.S.; Ding, H.; Koh, J.L.; Toufighi, K.; Mostafavi, S. et al. The genetic landscape of a cell. Science 2010, 327, 425-431.