Stress, drugs, and evolution: The role of cellular signaling in fungal drug resistance

Eukaryotic Cell

Volumn 7, Issue 5, 2008, Pages 747-764

  Cowen, Leah E ^a   Steinbach, William J ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT;

ANTIFUNGAL RESISTANCE; ASPERGILLUS FUMIGATUS; CANDIDA ALBICANS; CELL MEMBRANE; CELL WALL; CRYPTOCOCCUS NEOFORMANS; DRUG EFFECT; HUMAN; MOLECULAR EVOLUTION; MYCOSIS; PHYSIOLOGY; SHORT SURVEY; SIGNAL TRANSDUCTION;

ANTIBIOTICS, ANTIFUNGAL; ASPERGILLUS FUMIGATUS; CANDIDA ALBICANS; CELL MEMBRANE; CELL WALL; CRYPTOCOCCUS NEOFORMANS; DRUG RESISTANCE, FUNGAL; EVOLUTION, MOLECULAR; HUMANS; MYCOSES; SIGNAL TRANSDUCTION;

EID: 47049090269     PISSN: 15359778     EISSN: None     Source Type: Journal    
DOI: 10.1128/EC.00041-08     Document Type: Short Survey

References (243)

1. Abruzzo, G. K., A. M. Flattery, C. J. Gill, L. Kong, J. G. Smith, V. B. Pikounis, J. M. Balkovec, A. F. Bouffard, J. F. Dropinski, H. Rosen, H. Kropp, and K. Bartizal. 1997. Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis. Antimicrob. Agents Chemother. 41:2333-2338.
2. Aller, A. I., R. Claro, C. Castro, C. Serrano, M. F. Colom, and E. Martin-Mazuelos. 2007. Antifungal susceptibility of Cryptococcus neoformans isolates in HIV-infected patients to fluconazole, itraconazole and voriconazole in Spain: 1994-1996 and 1997-2005. Chemotherapy 53:300-305.
3. Anderson, J. B. 2005. Evolution of antifungal-drug resistance: mechanisms and pathogen fitness. Nat. Rev. Microbiol. 3:547-556.
4. Araujo, R., C. Pina-Vaz, and A. Goncalves Rodrigues. 2007. Susceptibility of environmental versus clinical strains of pathogenic Aspergillus. Int. J. Antimicrob. Agents 29:108-111.
5. Armengou, A., C. Porcar, J. Mascaro, and F. Garcia-Bragado. 1996. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin. Infect. Dis. 23:1337-1338.
6. Azam, M., and G. Q. Daley. 2006. Anticipating clinical resistance to target-directed agents: the BCR-ABL paradigm. Mol. Diagn. Ther. 10:67-76.
7. Bachmann, S. P., T. F. Patterson, and J. L. Lopez-Ribot. 2002. In vitro activity of caspofungin (MK-0991) against Candida albicans clinical isolates displaying different mechanisms of azole resistance. J. Clin. Microbiol. 40:2228-2230.
8. Bahn, Y. S., K. Kojima, G. M. Cox, and J. Heitman. 2006. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol. Biol. Cell 17:3122-3135.
9. Bahn, Y. S., C. Xue, A. Idnurm, J. C. Rutherford, J. Heitman, and M. E. Cardenas. 2007. Sensing the environment: lessons from fungi. Nat. Rev. Microbiol. 5:57-69.
10. Balashov, S. V., R. Gardiner, S. Park, and D. S. Perlin. 2005. Rapid, high-throughput, multiplex, real-time PCR for identification of mutations in the cyp51A gene of Aspergillus fumigatus that confer resistance to itraconazole. J. Clin. Microbiol. 43:214-222.
11. Balashov, S. V., S. Park, and D. S. Perlin. 2006. Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob. Agents Chemother. 50:2058-2063.
12. Baldauf, S. L., A. J. Roger, I. Wenk-Siefert, and W. F. Doolittle. 2000. A kingdom-level phylogeny of eukaryotes based on combined protein data. Science 290:972-977.
13. Bartizal, K., C. J. Gill, G. K. Abruzzo, A. M. Flattery, L. Kong, P. M. Scott, J. G. Smith, C. E. Leighton, A. Bouffard, J. F. Dropinski, and J. Balkovec. 1997. In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743,872). Antimicrob. Agents Chemother. 41:2326-2332.
14. Bennett, J. W., and K. T. Chung. 2001. Alexander Fleming and the discovery of penicillin. Adv. Appl. Microbiol. 49:163-184.
15. Berg, J., C. J. Clancy, and M. H. Nguyen. 1998. The hidden danger of primary fluconazole prophylaxis for patients with AIDS. Clin. Infect. Dis. 26:186-187.
16. Bii, C. C., K. Makimura, S. Abe, H. Taguchi, O. M. Mugasia, G. Revathi, N. C. Wamae, and S. Kamiya. 2007. Antifungal drug susceptibility of Cryptococcus neoformans from clinical sources in Nairobi, Kenya. Mycoses 50:25-30.
17. Birley, H. D., E. M. Johnson, P. McDonald, C. Parry, P. B. Carey, and D. W. Warnock. 1995. Azole drug resistance as a cause of clinical relapse in AIDS patients with cryptococcal meningitis. Int. J. STD AIDS 6:353-355.
18. Blankenship, J. R., and J. Heitman. 2005. Calcineurin is required for Candida albicans to survive calcium stress in serum. Infect. Immun. 73:5767-5774.
19. Blankenship, J. R., and A. P. Mitchell. 2006. How to build a biofilm: a fungal perspective. Curr. Opin. Microbiol. 9:588-594.
20. Blankenship, J. R., W. J. Steinbach, J. R. Perfect, and J. Heitman. 2003. Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs. Curr. Opin. Investig. Drugs 4:192-199.
21. Blankenship, J. R., F. L. Wormley, M. K. Boyce, W. A. Schell, S. G. Filler, J. R. Perfect, and J. Heitman. 2003. Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot. Cell 2:422-430.
22. Brion, L. P., S. E. Uko, and D. L. Goldman. 2007. Risk of resistance associated with fluconazole prophylaxis: systematic review. J. Infect. 54:521-529.
23. Bruno, V. M., and A. P. Mitchell. 2005. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol. Microbiol. 56:559-573.
24. Butler, M. S., and A. D. Buss. 2006. Natural products - the future scaffolds for novel antibiotics? Biochem. Pharmacol. 71:919-929.
25. Camilli, A., and B. L. Bassler. 2006. Bacterial small-molecule signaling pathways. Science 311:1113-1116.
26. 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.
27. Chauhan, N., M. Kruppa, and R. Calderone. 2007. The Ssk1p response regulator and Chk1p histidine kinase mutants of Candida albicans are hypersensitive to fluconazole and voriconazole. Antimicrob. Agents Chemother. 51:3747-3751.
28. Chayakulkeeree, M., and J. R. Perfect. 2006. Cryptococcosis. Infect. Dis. Clin. N. Am. 20:507-544.
29. 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.
30. Coste, A., V. Turner, F. Ischer, J. Morschhauser, A. Forche, A. Selmecki, J. Berman, J. Bille, and D. Sanglard. 2006. A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans. Genetics 172:2139-2156.
31. 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.
32. Cowen, L. E. 2008. The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype. Nat. Rev. Microbiol. 6:187-198.
33. Cowen, L. E., J. B. Anderson, and L. M. Kohn. 2002. Evolution of drug resistance in Candida albicans. Annu. Rev. Microbiol. 56:139-165.
34. Cowen, L. E., A. E. Carpenter, O. Matangkasombut, G. R. Fink, and S. Lindquist. 2006. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot. Cell 5:2184-2188.
35. Cowen, L. E., L. M. Kohn, and J. B. Anderson. 2001. Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 183:2971-2978.
36. Cowen, L. E., and S. Lindquist. 2005. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309:2185-2189.
37. Cowen, L. E., A. Nantel, M. S. Whiteway, D. Y. Thomas, D. C. Tessier, L. M. Kohn, and J. B. Anderson. 2002. Population genomics of drug resistance in Candida albicans. Proc. Natl. Acad. Sci. USA 99:9284-9289.
38. 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.
39. Cruz, M. C., A. L. Goldstein, J. R. Blankenship, M. Del Poeta, D. Davis, M. E. Cardenas, J. R. Perfect, J. H. McCusker, and J. Heitman. 2002. Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J. 21:546-559.
40. Cuenca-Estrella, M., T. M. Díaz-Guerra, E. Mellado, A. Monzón, and J. L. Rodríguez-Tudela. 1999. Comparative in vitro activity of voriconazole and itraconazole against fluconazole- susceptible and fluconazole-resistant clinical isolates of Candida species from Spain. Eur. J. Clin. Microbiol. Infect. Dis. 18:432-435.
41. Cuenca-Estrella, M., A. Gomez-Lopez, G. Garcia-Effron, L. Alcazar-Fuoli, E. Mellado, M. J. Buitrago, and J. L. Rodriguez-Tudela. 2005. Combined activity in vitro of caspofungin, amphotericin B, and azole agents against itraconazole-resistant clinical isolates of Aspergillus fumigatus. Antimicrob. Agents Chemother. 49:1232-1235.
42. Cuenca-Estrella, M., A. Gomez-Lopez, E. Mellado, M. J. Buitrago, A. Monzon, and J. L. Rodriguez-Tudela. 2006. Head-to-head comparison of the activities of currently available antifungal agents against 3,378 Spanish clinical isolates of yeasts and filamentous fungi. Antimicrob. Agents Chemother. 50:917-921.
43. Dannaoui, E., E. Borel, M. F. Monier, M. A. Piens, S. Picot, and F. Persat. 2001. Acquired itraconazole resistance in Aspergillus fumigatus. J. Antimicrob. Chemother. 47:333-340.
44. Dannaoui, E., E. Borel, F. Persat, M. F. Monier, and M. A. Piens. 1999. In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. EBGA Network. European research group on Biotypes and Genotypes of Aspergillus fumigatus. J. Med. Microbiol. 48:1087-1093.
45. Dannaoui, E., J. Meletiadis, A. M. Tortorano, F. Symoens, N. Nolard, M. A. Viviani, M. A. Piens, B. Lebeau, P. E. Verweij, and R. Grillot. 2004. Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered from treated patients. J. Med. Microbiol. 53:129-134.
46. Dannaoui, E., F. Persat, E. Borel, M. A. Piens, and S. Picot. 2001. Sterol composition of itraconazole-resistant and itraconazole-susceptible isolates of Aspergillus fumigatus. Can. J. Microbiol. 47:706-710.
47. da Silva Ferreira, M. E., J. L. Capellaro, E. dos Reis Marques, I. Malavazi, D. Perlin, S. Park, J. B. Anderson, A. L. Colombo, B. A. Arthington-Skaggs, M. H. Goldman, and G. H. Goldman. 2004. In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob. Agents Chemother. 48:4405-4413.
48. Del Poeta, M., M. C. Cruz, M. E. Cardenas, J. R. Perfect, and J. Heitman. 2000. Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob. Agents Chemother. 44:739-746.
49. De Lucca, A. J. 2007. Harmful fungi in both agriculture and medicine. Rev. Iberoam. Micol. 24:3-13.
50. Demeule, M., R. M. Wenger, and R. Beliveau. 1997. Molecular interactions of cyclosporin A with P-glycoprotein. Photolabeling with cyclosporin derivatives. J. Biol. Chem. 272:6647-6652.
51. de Micheli, M., J. Bille, C. Schueller, and D. Sanglard. 2002. A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance. Mol. Microbiol. 43:1197-1214.
52. d'Enfert, C. 2006. Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. Curr. Drug Targets 7:465-470.
53. Denning, D. W. 2003. Echinocandin antifungal drugs. Lancet 362:1142-1151.
54. Denning, D. W., K. A. Marr, W. M. Lau, D. P. Facklam, V. Ratanatharathorn, C. Becker, A. J. Ullmann, N. L. Seibel, P. M. Flynn, J. A. van Burik, D. N. Buell, and T. F. Patterson. 2006. Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis. J. Infect. 53:337-349.
55. Denning, D. W., S. A. Radford, K. L. Oakley, L. Hall, E. M. Johnson, and D. W. Warnock. 1997. Correlation between in-vitro susceptibility testing to itraconazole and in-vivo outcome of Aspergillus fumigatus infection. J. Antimicrob. Chemother. 40:401-414.
56. Denning, D. W., K. Venkateswarlu, K. L. Oakley, M. J. Anderson, N. J. Manning, D. A. Stevens, D. W. Warnock, and S. L. Kelly. 1997. Itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 41:1364-1368.
57. Diaz-Guerra, T. M., E. Mellado, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2003. A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 47:1120-1124.
58. Douglas, C. M., J. A. D'Ippolito, G. J. Shei, M. Meinz, J. Onishi, J. A. Marrinan, W. Li, G. K. Abruzzo, A. Flattery, K. Bartizal, A. Mitchell, and M. B. Kurtz. 1997. Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-β-D-glucan synthase inhibitors. Antimicrob. Agents Chemother. 41:2471-2479.
59. Douglas, C. M., F. Foor, J. A. Marrinan, N. Morin, J. B. Nielsen, A. M. Dahl, P. Mazur, W. Baginsky, W. Li, M. el-Sherbeini, et al. 1994. The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-beta-D-glucan synthase. Proc. Natl. Acad. Sci. USA 91:12907-12911.
60. Douglas, C. M., J. A. Marrinan, W. Li, and M. B. Kurtz. 1994. A Saccharomyces cerevisiae mutant with echinocandin-resistant 1,3-β-D-glucan synthase. J. Bacteriol. 176:5686-5696.
61. Du, W., M. Coaker, J. D. Sobel, and R. A. Akins. 2004. Shuttle vectors for Candida albicans: control of plasmid copy number and elevated expression of cloned genes. Curr. Genet. 45:390-398.
62. Ellis, D. 2002. Amphotericin B: spectrum and resistance. J. Antimicrob. Chemother. 49(Suppl. 1):7-10.
63. Eng, W. K., L. Faucette, M. M. McLaughlin, R. Cafferkey, Y. Koltin, R. A. Morris, P. R. Young, R. K. Johnson, and G. P. Livi. 1994. The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth. Gene 151:61-71.
64. Eschertzhuber, S., C. Velik-Salchner, C. Hoermann, D. Hoefer, and C. Lass-Florl. 1 July 2007. Caspofungin-resistant Aspergillus flavus after heart transplantation and mechanical circulatory support: a case report. Transpl. Infect. Dis. doi:10.1111/j.1399-3062.2007.00252.x.
65. Feldmesser, M., Y. Kress, A. Mednick, and A. Casadevall. 2000. The effect of the echinocandin analogue caspofungin on cell wall glucan synthesis by Cryptococcus neoformans. J. Infect. Dis. 182:1791-1795.
66. Fox, D. S., and J. Heitman. 2002. Good fungi gone bad: the corruption of calcineurin. Bioessays 24:894-903.
67. Franz, R., S. L. Kelly, D. C. Lamb, D. E. Kelly, M. Ruhnke, and J. Morschhauser. 1998. Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains. Antimicrob. Agents Chemotherapy. 42:3065-3072.
68. Franzot, S. P., and A. Casadevall. 1997. Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole against Cryptococcus neoformans in vitro. Antimicrob. Agents Chemother. 41:331-336.
69. Garcia-Effron, G., E. Mellado, A. Gomez-Lopez, L. Alcazar-Fuoli, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2005. Differences in interactions between azole drugs related to modifications in the 14-α sterol demethylase gene (cyp51A) of Aspergillus fumigatus. Antimicrob. Agents Chemother. 49:2119-2121.
70. Gardiner, R. E., P. Souteropoulos, S. Park, and D. S. Perlin. 2005. Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin. Med. Mycol. 43(Suppl. 1):299-305.
71. Graybill, J. R., S. Hernandez, R. Bocanegra, and L. K. Najvar. 2004. Antifungal therapy of murine Aspergillus terreus infection. Antimicrob. Agents Chemother. 48:3715-3719.
72. Gulshan, K., and W. S. Moye-Rowley. 2007. Multidrug resistance in fungi. Eukaryot. Cell 6:1933-1942.
73. Gunatilaka, A. A. 2006. Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J. Nat. Prod. 69:509-526.
74. Higgins, C. F. 2007. Multiple molecular mechanisms for multidrug resistance transporters. Nature 446:749-757.
75. Hiller, D., S. Stahl, and J. Morschhauser. 2006. Multiple cis-acting sequences mediate upregulation of the MDR1 efflux pump in a fluconazoleresistant clinical Candida albicans isolate. Antimicrob. Agents Chemother. 50:2300-2308.
76. Hogan, D. A. 2006. Talking to themselves: autoregulation and quorum sensing in fungi. Eukaryot. Cell 5:613-619.
77. Howard, S. J., I. Webster, C. B. Moore, R. E. Gardiner, S. Park, D. S. Perlin, and D. W. Denning. 2006. Multi-azole resistance in Aspergillus fumigatus. Int. J. Antimicrob. Agents 28:450-453.
78. Imai, J., and I. Yahara. 2000. Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin. Mol. Cell. Biol. 20:9262-9270.
79. Jachez, B., D. Boesch, M. A. Grassberger, and F. Loor. 1993. Reversion of the P-glycoprotein-mediated multidrug resistance of cancer cells by FK-506 derivatives. Anticancer Drugs 4:223-229.
80. Jain, P., I. Akula, and T. Edlind. 2003. Cyclic AMP signaling pathway modulates susceptibility of Candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Antimicrob. Agents Chemother. 47:3195-3201.
81. Johnson, E. M., K. L. Oakley, S. A. Radford, C. B. Moore, P. Warn, D. W. Warnock, and D. W. Denning. 2000. Lack of correlation of in vitro amphotericin B susceptibility testing with outcome in a murine model of Aspergillus infection. J. Antimicrob. Chemother. 45:85-93.
82. Joseph-Horne, T., D. Hollomon, R. S. Loeffler, and S. L. Kelly. 1995. Cross-resistance to polyene and azole drugs in Cryptococcus neoformans. Antimicrob. Agents Chemother. 39:1526-1529.
83. Kafadar, K. A., and M. S. Cyert. 2004. Integration of stress responses: modulation of calcineurin signaling in Saccharomyces cerevisiae by protein kinase A. Eukaryot. Cell 3:1147-1153.
84. Karababa, M., E. Valentino, G. Pardini, A. T. Coste, J. Bille, and D. Sanglard. 2006. CRZ1, a target of the calcineurin pathway in Candida albicans. Mol. Microbiol. 59:1429-1451.
85. Kauffman, C. A. 2006. Clinical efficacy of new antifungal agents. Curr. Opin. Microbiol. 9:483-488.
86. Keller, N. P., G. Turner, and J. W. Bennett. 2005. Fungal secondary metabolism: from biochemistry to genomics. Nat. Rev. Microbiol. 3:937-947.
87. 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 crossresistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6-desaturation. FEBS Lett. 400:80-82.
88. Kelly, S. L., D. C. Lamb, M. Taylor, A. J. Corran, B. C. Baldwin, and W. G. Powderly. 1994. Resistance to amphotericin B associated with defective sterol delta 8->7 isomerase in a Cryptococcus neoformans strain from an AIDS patient. FEMS Microbiol. Lett. 122:39-42.
89. Kojima, K., Y. S. Bahn, and J. Heitman. 2006. Calcineurin, Mpk1 and Hog1 MAPK pathways independently control fludioxonil antifungal sensitivity in Cryptococcus neoformans. Microbiology 152:591-604.
90. Kontoyiannis, D. P., R. E. Lewis, G. S. May, N. Osherov, and M. G. Rinaldi. 2002. Aspergillus nidulans is frequently resistant to amphotericin B. Mycoses 45:406-407.
91. Kontoyiannis, D. P., R. E. Lewis, N. Osherov, N. D. Albert, and G. S. May. 2003. Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J. Antimicrob. Chemother. 51:313-316.
92. Kraus, P. R., D. S. Fox, G. M. Cox, and J. Heitman. 2003. The Cryptococcus neoformans MAP kinase Mpk1 regulates cell integrity in response to antifungal drugs and loss of calcineurin function. Mol. Microbiol. 48:1377-1387.
93. Krishnarao, T. V., and J. N. Galgiani. 1997. Comparison of the in vitro activities of the echinocandin LY303366, the pneumocandin MK-0991, and fluconazole against Candida species and Cryptococcus neoformans. Antimicrob. Agents Chemother. 41:1957-1960.
94. Kullas, A. L., S. J. Martin, and D. Davis. 2007. Adaptation to environmental pH: integrating the Rim101 and calcineurin signal transduction pathways. Mol. Microbiol. 66:858-871.
95. Kumar, R., A. Musiyenko, and S. Barik. 2005. Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin. Mol. Biochem. Parasitol. 141:29-37.
96. Kurtz, M. B., G. Abruzzo, A. Flattery, K. Bartizal, J. A. Marrinan, W. Li, J. Milligan, K. Nollstadt, and C. M. Douglas. 1996. Characterization of echinocandin-resistant mutants of Candida albicans: genetic, biochemical, and virulence studies. Infect. Immun. 64:3244-3251.
97. Lam, K. S. 2007. New aspects of natural products in drug discovery. Trends Microbiol. 15:279-289.
98. 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.
99. Lambert, P. A. 2005. Bacterial resistance to antibiotics: modified target sites. Adv. Drug Deliv. Rev. 57:1471-1485.
100. Lass-Flörl, C., K. Griff, A. Mayr, A. Petzer, G. Gastl, H. Bonatti, M. Freund, G. Kropshofer, M. P. Dierich, and D. Nachbaur. 2005. Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. Br. J. Haematol. 131:201-207.
101. Lass-Flörl, C., G. Kofler, G. Kropshofer, J. Hermans, A. Kreczy, M. P. Dierich, and D. Niederwieser. 1998. In-vitro testing of susceptibility to amphotericin B is a reliable predictor of clinical outcome in invasive aspergillosis. J. Antimicrob. Chemother. 42:497-502.
102. Latge, J. P., I. Mouyna, F. Tekaia, A. Beauvais, J. P. Debeaupuis, and W. Nierman. 2005. Specific molecular features in the organization and biosynthesis of the cell wall of Aspergillus fumigatus. Med. Mycol. 43(Suppl. 1):S15-S22.
103. Laverdiere, M., R. G. Lalonde, J. G. Baril, D. C. Sheppard, S. Park, and D. S. Perlin. 2006. Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis. J. Antimicrob. Chemother. 57:705-708.
104. Lesage, G., and H. Bussey. 2006. Cell wall assembly in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 70:317-343.
105. Lesage, G., A. M. Sdicu, P. Menard, J. Shapiro, S. Hussein, and H. Bussey. 2004. Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin. Genetics 167:35-49.
106. Levin, D. E. 2005. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 69:262-291.
107. Liebmann, B., M. Müller, A. Braun, and A. A. Brakhage. 2004. The cyclic AMP-dependent protein kinase A network regulates development and virulence in Aspergillus fumigatus. Infect. Immun. 72:5193-5203.
108. Lionakis, M. S., R. E. Lewis, G. Chamilos, and D. P. Kontoyiannis. 2005. Aspergillus suceptibility testing in patients with cancer and invasive aspergillosis: difficulties in establishing correlation between in vitro susceptibility data and the outcome of initial amphotericin B therapy. Pharmacotherapy 25:1174-1180.
109. Liu, J., J. D. Farmer, Jr., W. S. Lane, J. Friedman, I. Weissman, and S. L. Schreiber. 1991. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66:807-815.
110. Liu, T. T., R. E. Lee, K. S. Barker, R. E. Lee, L. Wei, R. Homayouni, and P. D. Rogers. 2005. Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Antimicrob. Agents Chemother. 49:2226-2236.
111. 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.
112. Lupetti, A., R. Danesi, M. Campa, M. Del Tacca, and S. Kelly. 2002. Molecular basis of resistance to azole antifungals. Trends Mol. Med. 8:76-81.
113. Maidan, M. M., L. De Rop, J. Serneels, S. Exler, S. Rupp, H. Tournu, J. M. Thevelein, and P. Van Dijck. 2005. The G protein-coupled receptor Gpr1 and the Galpha protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans. Mol. Biol. Cell 16:1971-1986.
114. Maligie, M. A., and C. P. Selitrennikoff. 2005. Cryptococcus neoformans resistance to echinocandins: (1,3)β-glucan synthase activity is sensitive to echinocandins. Antimicrob. Agents Chemother. 49:2851-2856.
115. Manavathu, E. K., O. C. Abraham, and P. H. Chandrasekar. 2001. Isolation and in vitro susceptibility to amphotericin B, itraconazole and posaconazole of voriconazole-resistant laboratory isolates of Aspergillus fumigatus. Clin. Microbiol. Infect. 7:130-137.
116. Manavathu, E. K., J. A. Vazquez, and P. H. Chandrasekar. 1999. Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent. Int. J. Antimicrob. Agents 12:213-219.
117. Mann, P. A., R. M. Parmegiani, S.-Q. Wei, C. A. Mendrick, X. Li, D. Loebenberg, B. DiDomenico, R. S. Hare, S. S. Walker, and P. M. McNicholas. 2003. Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14α-demethylase. Antimicrob. Agents Chemother. 47:577-581.
118. Marchetti, O., J. M. Entenza, D. Sanglard, J. Bille, M. P. Glauser, and P. Moreillon. 2000. Fluconazole plus cyclosporine: a fungicidal combination effective against experimental endocarditis due to Candida albicans. Antimicrob. Agents Chemother. 44:2932-2938.
119. Marchetti, O., P. Moreillon, J. M. Entenza, J. Vouillamoz, M. P. Glauser, J. Bille, and D. Sanglard. 2003. Fungicidal synergism of fluconazole and cyclosporine in Candida albicans is not dependent on multidrug efflux transporters encoded by the CDR1, CDR2, CaMDR1, and FLU1 genes. Antimicrob. Agents Chemother. 47:1565-1570.
120. 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.
121. Marichal, P., L. Koymans, S. Willemsens, D. Bellens, P. Verhasselt, W. Luyten, M. Borgers, F. C. Ramaekers, F. C. Odds, and H. V. Bossche. 1999. Contribution of mutations in the cytochrome P450 14alpha-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Microbiology 145:2701-2713.
122. Markovich, S., A. Yekutiel, I. Shalit, Y. Shadkchan, and N. Osherov. 2004. Genomic approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 48:3871-3876.
123. Martin, G. S., D. M. Mannino, S. Eaton, and M. Moss. 2003. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med. 348:1546-1554.
124. Martinez, L. R., and A. Casadevall. 2006. Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro. Antimicrob. Agents Chemother. 50:1021-1033.
125. Martinez-Lopez, R., L. Monteoliva, R. Diez-Orejas, C. Nombela, and C. Gil. 2004. The GPI-anchored protein CaEcm33p is required for cell wall integrity, morphogenesis and virulence in Candida albicans. Microbiology 150:3341-3354.
126. Matthews, R. C., G. Rigg, S. Hodgetts, T. Carter, C. Chapman, C. Gregory, C. Illidge, and J. Burnie. 2003. Preclinical assessment of the efficacy of Mycograb, a human recombinant antibody against fungal HSP90. Antimicrob. Agents Chemother. 47:2208-2216.
127. May, G. S., T. Xue, D. P. Kontoyiannis, and M. C. Gustin. 2005. Mitogen activated protein kinases of Aspergillus fumigatus. Med. Mycol. 43:583-586.
128. Mazur, P., N. Morin, W. Baginsky, M. el-Sherbeini, J. A. Clemas, J. B. Nielsen, and F. Foor. 1995. Differential expression and function of two homologous subunits of yeast 1,3-β-D-glucan synthase. Mol. Cell. Biol. 15:5671-5681.
129. McNeil, M. M., S. L. Nash, R. A. Hajjeh, M. A. Phelan, L. A. Conn, B. D. Plikaytis, and D. W. Warnock. 2001. Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997. Clin. Infect. Dis. 33:641-647.
130. Mellado, E., T. M. Diaz-Guerra, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2001. Identification of two different 14-α sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J. Clin. Microbiol. 39:2431-2438.
131. Mellado, E., G. Garcia-Effron, L. Alcazar-Fuoli, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2004. Substitutions at methionine 220 in the 14α-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob. Agents Chemother. 48:2747-2750.
132. Mellado, E., G. Garcia-Effron, L. Alcázar-Fuoli, W. J. Melchers, P. E. Verweij, M. Cuenca-Estrella, and J. L. Rodríguez- Tudela. 2007. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob. Agents Chemother. 51:1897-1904.
133. Messer, S. A., R. N. Jones, and T. R. Fritsche. 2006. International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003). J. Clin. Microbiol. 44:1782-1787.
134. Miller, C. D., B. W. Lomaestro, S. Park, and D. S. Perlin. 2006. Progressive esophagitis caused by Candida albicans with reduced susceptibility to caspofungin. Pharmacotherapy 26:877-880.
135. Miyazaki, T., Y. Miyazaki, K. Izumikawa, H. Kakeya, S. Miyakoshi, J. E. Bennett, and S. Kohno. 2006. Fluconazole treatment is effective against a Candida albicans erg3/erg3 mutant in vivo despite in vitro resistance. Antimicrob. Agents Chemother. 50:580-586.
136. Mondon, P., R. Petter, G. Amalfitano, R. Luzzati, E. Concia, I. Polacheck, and K. J. Kwon-Chung. 1999. Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans. Antimicrob. Agents Chemother. 43:1856-1861.
137. Moosa, M.-Y. S., G. J. Alangaden, E. Manavathu, and P. H. Chandrasekar. 2002. Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis. J. Antimicrob. Chemother. 49:209-213.
138. Mora-Duarte, J., R. Betts, C. Rotstein, A. L. Colombo, L. Thompson-Moya, J. Smietana, R. Lupinacci, C. Sable, N. Kartsonis, and J. Perfect. 2002. Comparison of caspofungin and amphotericin B for invasive candidiasis. N. Engl. J. Med. 347:2020-2029.
139. Morschhauser, J., K. S. Barker, T. T. Liu, B. W. J. Bla, 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.
140. Munro, C. A., S. Selvaggini, I. de Bruijn, L. Walker, M. D. Lenardon, B. Gerssen, S. Milne, A. J. Brown, and N. A. Gow. 2007. The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol. Microbiol. 63:1399-1413.
141. Nascimento, A. M., G. H. Goldman, S. Park, S. A. Marras, G. Delmas, U. Oza, K. Lolans, M. N. Dudley, P. A. Mann, and D. S. Perlin. 2003. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob. Agents Chemother. 47:1719-1726.
142. Nett, J., and D. Andes. 2006. Candida albicans biofilm development, modeling a host-pathogen interaction. Curr. Opin. Microbiol. 9:340-345.
143. Nett, J., L. Lincoln, K. Marchillo, R. Massey, K. Holoyda, B. Hoff, M. VanHandel, and D. Andes. 2007. Putative role of β-1,3 glucans in Candida albicans biofilm resistance. Antimicrob. Agents Chemother. 51:510-520.
144. 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.
145. Nobile, C. J., and A. P. Mitchell. 2006. Genetics and genomics of Candida albicans biofilm formation. Cell. Microbiol. 8:1382-1391.
146. Nolte, 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.
147. Odds, F. C., A. J. Brown, and N. A. Gow. 2003. Antifungal agents: mechanisms of action. Trends Microbiol. 11:272-279.
148. Odds, F. C., V. F. Gerven, A. Espinel-Ingroff, M. S. Bartlett, M. A. Ghannoum, M. V. Lancaster, M. A. Pfaller, J. H. Rex, M. G. Rinaldi, and T. J. Walsh. 1998. Evaluation of possible correlation between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob. Agents Chemother. 42:282-288.
149. Oliver, B. G., J. C. Panepinto, J. R. Fortwendel, D. L. Smith, D. S. Askew, and J. C. Rhodes. 2002. Cloning and expression of pkaC and pkaR, the genes encoding the cAMP-dependent protein kinase of Aspergillus fumigatus. Mycopathologica 154:85-91.
150. Onyewu, C., J. R. Blankenship, M. Del Poeta, and J. Heitman. 2003. Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob. Agents Chemother. 47:956-964.
151. Onyewu, C., F. L. Wormley, Jr., J. R. Perfect, and J. Heitman. 2004. The calcineurin target, Crz1, functions in azole tolerance but is not required for virulence of Candida albicans. Infect. Immun. 72:7330-7333.
152. Osherov, N., D. P. Kontoyiannis, A. Romans, and G. S. May. 2001. Resistance to itraconazole in Aspergillus nidulans and Aspergillus fumigatus is conferred by extra copies of the A. nidulans P-450 14alpha-demethylase gene, pdmA. J. Antimicrob. Chemother. 48:75-81.
153. Ostrosky-Zeichner, L., D. Kontoyiannis, J. Raffalli, K. M. Mullane, J. Vazquez, E. J. Anaissie, J. Lipton, P. Jacobs, J. H. van Rensburg, J. H. Rex, W. Lau, D. Facklam, and D. N. Buell. 2005. International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia. Eur. J. Clin. Microbiol. Infect. Dis. 24:654-661.
154. Pachl, J., P. Svoboda, F. Jacobs, K. Vandewoude, B. van der Hoven, P. Spronk, G. Masterson, M. Malbrain, M. Aoun, J. Garbino, J. Takala, L. Drgona, J. Burnie, and R. Matthews. 2006. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin. Infect. Dis. 42:1404-1413.
155. Paderu, P., G. Garcia-Effron, S. Balashov, G. Delmas, S. Park, and D. S. Perlin. 2007. Serum differentially alters the antifungal properties of echinocandin drugs. Antimicrob. Agents Chemother. 51:2253-2256.
156. Pan, X., and J. Heitman. 1999. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol. Cell. Biol. 19:4874-4887.
157. Pardo, M., L. Monteoliva, P. Vázquez, R. Martínez, G. Molero, C. Nombela, and C. Gil. 2004. PST1 and ECM33 encode two yeast cell surface GPI proteins important for cell wall integrity. Microbiology 150:4157-4170.
158. Park, S., R. Kelly, J. N. Kahn, J. Robles, M. J. Hsu, E. Register, W. Li, V. Vyas, H. Fan, G. Abruzzo, A. Flattery, C. Gill, G. Chrebet, S. A. Parent, M. Kurtz, H. Teppler, C. M. Douglas, and D. S. Perlin. 2005. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob. Agents Chemother. 49:3264-3273.
159. + transport. Eukaryot. Cell 6:443-453.
160. Pasticci, M. B., F. Barchiesi, S. Fallani, N. Palladino, L. M. Lapalorcia, M. Gubbiotti, M. Cozzari, A. Novelli, and F. Baldelli. 2006. Clinical efficacy and tolerability of caspofungin in a renal transplant patient with Aspergillus flavus lung infection: case report. J. Chemother. 18:549-553.
161. Paugam, A., J. Dupouy-Camet, P. Blanche, J. P. Gangneux, C. Tourte-Schaefer, and D. Sicard. 1994. Increased fluconazole resistance of Cryptococcus neoformans isolated from a patient with AIDS and recurrent meningitis. Clin. Infect. Dis. 19:975-976.
162. Pearl, L. H., and C. Prodromou. 2006. Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu. Rev. Biochem. 75:271-294.
163. 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.
164. Perfect, J. R., and G. M. Cox. 1999. Drug resistance in Cryptococcus neoformans. Drug Resist. Updates 2:259-269.
165. Perlin, D. S. 2007. Resistance to echinocandin-class antifungal drugs. Drug Resist. Updates 10:121-130.
166. Pfaller, M., J. Riley, and T. Koerner. 1989. Effects of cilofungin (LY121019) on carbohydrate and sterol composition of Candida albicans. Eur. J. Clin. Microbiol. Infect. Dis. 8:1067-1070.
167. Pfaller, M. A., L. Boyken, R. J. Hollis, S. A. Messer, S. Tendolkar, and D. J. Diekema. 2005. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. J. Clin. Microbiol. 43:5425-5427.
168. Pfaller, M. A., and D. J. Diekema. 2004. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol. 42:4419-4431.
169. Pfaller, M. A., and D. J. Diekema. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20:133-163.
170. Pfaller, M. A., D. J. Diekema, S. A. Messer, R. J. Hollis, and R. N. Jones. 2003. In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates. Antimicrob. Agents Chemother. 47:1068-1071.
171. Pfaller, M. A., S. A. Messer, L. Boyken, C. Rice, S. Tendolkar, R. J. Hollis, and D. J. Diekema. 2003. Caspofungin activity against clinical isolates of fluconazole-resistant Candida. J. Clin. Microbiol. 41:5729-5731.
172. Pfaller, M. A., S. A. Messer, L. Boyken, C. Rice, S. Tendolkar, R. J. Hollis, G. V. Doern, and D. J. Diekema. 2005. Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990 to 2004). J. Clin. Microbiol. 43:2163-2167.
173. Pfaller, M. A., S. A. Messer, R. J. Hollis, and R. N. Jones. 2002. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY antimicrobial surveillance program, 2000. Antimicrob. Agents Chemother. 46:1032-1037.
174. Picard, D. 2002. Heat-shock protein 90, a chaperone for folding and regulation. Cell. Mol. Life Sci. 59:1640-1648.
175. Piddock, L. J. 2006. Multidrug-resistance efflux pumps-not just for resistance. Nat. Rev. Microbiol. 4:629-636.
176. Posteraro, B., M. Sanguinetti, D. Sanglard, M. La Sorda, S. Boccia, L. Romano, G. Morace, and G. Fadda. 2003. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol. Microbiol. 47:357-371.
177. Pratt, W. B., and D. O. Toft. 2003. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp. Biol. Med. 228:111-133.
178. Qadota, H., C. P. Python, S. B. Inoue, M. Arisawa, Y. Anraku, Y. Zheng, T. Watanabe, D. E. Levin, and Y. Ohya. 1996. Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3-beta-glucan synthase. Science 272:279-281.
179. Rao, U. S., and G. A. Scarborough. 1994. Direct demonstration of high affinity interactions of immunosuppressant drugs with the drug binding site of the human P-glycoprotein. Mol. Pharmacol. 45:773-776.
180. Reboli, A. C., C. Rotstein, P. G. Pappas, S. W. Chapman, D. H. Kett, D. Kumar, R. Betts, M. Wible, B. P. Goldstein, J. Schranz, D. S. Krause, and T. Walsh. 2007. Anidulafungin versus fluconazole for invasive candidiasis. N. Engl. J. Med. 356:2472-2482.
181. Reinoso-Martin, C., C. Schuller, M. Schuetzer-Muehlbauer, and K. Kuchler. 2003. The yeast protein kinase C cell integrity pathway mediates tolerance to the antifungal drug caspofungin through activation of Slt2p mitogen-activated protein kinase signaling. Eukaryot. Cell 2:1200-1210.
182. Riggle, P. J., and C. A. Kumamoto. 2006. Transcriptional regulation of MDR1, encoding a drug efflux determinant, in fluconazole-resistant Candida albicans strains through an Mcm1p binding site. Eukaryot. Cell 5:1957-1968.
183. Riley, M. A., and J. E. Wertz. 2002. Bacteriocins: evolution, ecology, and application. Annu. Rev. Microbiol. 56:117-137.
184. Robertson, L. S., and G. R. Fink. 1998. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc. Natl. Acad. Sci. USA 95:13783-13787.
185. Rocha, E. M., G. Garcia-Effron, S. Park, and D. S. Perlin. 2007. A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob. Agents Chemother. 51:4174-4176.
186. Rodero, L., E. Mellado, A. C. Rodriguez, A. Salve, L. Guelfand, P. Cahn, M. Cuenca-Estrella, G. Davel, and J. L. Rodriguez-Tudela. 2003. G484S amino acid substitution in lanosterol 14-α demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate. Antimicrob. Agents Chemother. 47:3653-3656.
187. Roe, S. M., C. Prodromou, R. O'Brien, J. E. Ladbury, P. W. Piper, and L. H. Pearl. 1999. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J. Med. Chem. 42:260-266.
188. Rognon, B., Z. Kozovska, A. T. Coste, G. Pardini, and D. Sanglard. 2006. Identification of promoter elements responsible for the regulation of MDR1 from Candida albicans, a major facilitator transporter involved in azole resistance. Microbiology 152:3701-3722.
189. Romano, J., G. Nimrod, N. Ben-Tal, Y. Shadkchan, K. Baruch, H. Sharon, and N. Osherov. 2006. Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence. Microbiology 152:1919-1928.
190. 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.
191. Sanglard, D., F. Ischer, O. Marchetti, J. Entenza, and J. Bille. 2003. Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Mol. Microbiol. 48:959-976.
192. 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.
193. Santos, M., and I. F. de Larrinoa. 2005. Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor. Curr. Genet. 48:88-100.
194. Schimoler-O'Rourke, R., S. Renault, W. Mo, and C. P. Selitrennikoff. 2003. Neurospora crassa FKS protein binds to the (1,3)beta-glucan synthase substrate, UDP-glucose. Curr. Microbiol. 46:408-412.
195. Schreiber, S. L. 2005. Small molecules: the missing link in the central dogma. Nat. Chem. Biol. 1:64-66.
196. 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.
197. Schuetzer-Muehlbauer, M., B. Willinger, G. Krapf, S. Enzinger, E. Presterl, and K. Kuchler. 2003. The Candida albicans Cdr2p ATP-binding cassette (ABC) transporter confers resistance to caspofungin. Mol. Microbiol. 48:225-235.
198. Selmecki, A., A. Forche, and J. Berman. 2006. Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Science 313:367-370.
199. Selmecki, A., M. Gerami-Nejad, C. Paulson, A. Forche, and J. Berman. An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1. Mol. Microbiol., in press.
200. Sipos, G., and K. Kuchler. 2006. Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr. Drug Targets 7:471-481.
201. Slaven, J. W., M. J. Anderson, D. Sanglard, G. K. Dixon, J. Bille, I. S. Roberts, and D. Denning. 2002. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet. Biol. 36:199-206.
202. Stathopoulos, A. M., and M. S. Cyert. 1997. Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 11:3432-3444.
203. Steinbach, W. J., D. K. J. Benjamin, D. P. Kontoyiannis, J. R. Perfect, I. Lutsar, K. A. Marr, M. S. Lionakis, H. A. Torres, H. Jafri, and T. J. Walsh. 2004. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin. Infect. Dis. 39:192-198.
204. Steinbach, W. J., R. A. Cramer, Jr., B. Z. Perfect, Y. G. Asfaw, T. C. Sauer, L. K. Najvar, W. R. Kirkpatrick, T. F. Patterson, D. K. Benjamin, Jr., J. Heitman, and J. R. Perfect. 2006. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot. Cell 5:1091-1103.
205. Steinbach, W. J., R. A. Cramer, Jr., B. Z. Perfect, C. Henn, K. Nielsen, J. Heitman, and J. R. Perfect. 2007. Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus. Antimicrob. Agents Chemother. 51:2979-2981.
206. 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.
207. Steinbach, W. J., W. A. Schell, J. R. Blankenship, C. Onyewu, J. Heitman, and J. R. Perfect. 2004. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus. Antimicrob. Agents Chemother. 48:1664-1669.
208. Steinbach, W. J., N. Singh, J. L. Miller, D. K. Benjamin, Jr., W. A. Schell, J. Heitman, and J. R. Perfect. 2004. In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus isolates from transplant and nontransplant patients. Antimicrob. Agents Chemother. 48:4922-4925.
209. Steinbach, W. J., and D. A. Stevens. 2003. Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis. Clin. Infect. Dis. 37(Suppl. 3):S157-S187.
210. Sterling, T. R., and W. G. Merz. 1998. Resistance to amphotericin B: emerging clinical and microbiological patterns. Drug Resist. Updates 1:161-165.
211. Sternbach, G., and J. Varon. 1992. Alexander Fleming: the spectrum of penicillin. J. Emerg. Med. 10:89-91.
212. Stevens, D. A., M. Ichinomiya, Y. Koshi, and H. Horiuchi. 2006. Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for β-1,6-glucan synthesis inhibition by caspofungin. Antimicrob. Agents Chemother. 50:3160-3161.
213. Sutton, D. A., S. E. Sanchie, S. G. Revankar, A. W. Fothergill, and M. G. Rinaldi. 1999. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J. Clin. Microbiol. 37:2343-2345.
214. Szakacs, G., J. K. Paterson, J. A. Ludwig, C. Booth-Genthe, and M. M. Gottesman. 2006. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov. 5:219-234.
215. Thompson, J. R., C. M. Douglas, W. Li, C. K. Jue, B. Pramanik, X. Yuan, T. H. Rude, D. L. Toffaletti, J. R. Perfect, and M. Kurtz. 1999. A glucan synthase FKS1 homolog in Cryptococcus neoformans is single copy and encodes an essential function. J. Bacteriol. 181:444-453.
216. Thornewell, S. J., R. B. Peery, and P. L. Skatrud. 1997. Cloning and characterization of CneMDR1: a Cryptococcus neoformans gene encoding a protein related to multidrug resistance proteins. Gene 201:21-29.
217. Tobin, M. B., R. B. Peery, and P. L. Skatrud. 1997. Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene 200:11-23.
218. Trama, J. P., E. Mordechai, and M. E. Adelson. 2005. Detection of Aspergillus fumigatus and a mutation that confers reduced susceptibility to itraconazole and posaconazole by real-time PCR and pyrosequencing. J. Clin. Microbiol. 43:906-908.
219. Turner, M. S., R. H. Drew, and J. R. Perfect. 2006. Emerging echinocandins for treatment of invasive fungal infections. Expert Opin. Emerg. Drugs 11:231-250.
220. Valiante, V., T. Heinekamp, R. Jain, A. Härtl, and A. A. Brakhage. 25 September 2007. The mitogen-activated protein kinase MpkA of Aspergillus fumigatus regulates cell wall signaling and oxidative stress response. Fungal Genet. Biol. doi:10.1016/j.fgb.2007.09.006.
221. Venkateswarlu, K., M. Taylor, N. J. Manning, M. G. Rinaldi, and S. L. Kelly. 1997. Fluconazole tolerance in clinical isolates of Cryptococcus neoformans. Antimicrob. Agents Chemother. 41:748-751.
222. Verweij, P. E., E. Mellado, and W. J. Melchers. 2007. Multiple-triazoleresistant aspergillosis. N. Engl. J. Med. 356:1481-1483.
223. Walsh, T. J., V. Petraitis, R. Petraitiene, A. Field-Ridley, D. Sutton, M. Ghannoum, T. Sein, R. Schaufele, J. Peter, J. Bacher, H. Casler, D. Armstrong, A. Espinel-Ingroff, M. G. Rinaldi, and C. A. Lyman. 2003. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J. Infect. Dis. 188:305-319.
224. Walsh, T. J., M. A. Viviani, E. Arathoon, C. Chiou, M. Ghannoum, A. H. Groll, and F. C. Odds. 2000. New targets and delivery systems for antifungal therapy. Med. Mycol. 38:335-347.
225. Warn, P. A., G. Morrissey, J. Morrissey, and D. W. Denning. 2003. Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B. J. Antimicrob. Chemother. 51:913-919.
226. Warris, A., C. M. Weemaes, and P. E. Verweij. 2002. Multidrug resistance in Aspergillus fumigatus. N. Engl. J. Med. 347:2173-2174.
227. Weisberg, E., P. W. Manley, S. W. Cowan-Jacob, A. Hochhaus, and J. D. Griffin. 2007. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat. Rev. Cancer 7:345-356.
228. 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.
229. White, T. C., K. A. Marr, and R. A. Bowden. 1998. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin. Microbiol. Rev. 11:382-402.
230. White, T. C., M. A. Pfaller, M. G. Rinaldi, J. Smith, and S. W. Redding. 1997. Stable azole drug resistance associated with a substrain of Candida albicans from an HIV-infected patient. Oral Dis. 3(Suppl. 1):S102-S109.
231. Whitesell, L., E. G. Mimnaugh, B. De Costa, C. E. Myers, and L. M. Neckers. 1994. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. USA 91:8324-8328.
232. Wiederhold, N. P. 2007. Attenuation of echinocandin activity at elevated concentrations: a review of the paradoxical effect. Curr. Opin. Infect. Dis. 20:574-578.
233. Wiederhold, N. P., D. P. Kontoyiannis, R. A. Prince, and R. E. Lewis. 2005. Attenuation of the activity of caspofungin at high concentrations against Candida albicans: possible role of cell wall integrity and calcineurin pathways. Antimicrob. Agents Chemother. 49:5146-5148.
234. Wilson, L. S., C. M. Reyes, M. Stolpman, J. Speckman, K. Allen, and J. Beney. 2002. The direct cost and incidence of systemic fungal infections. Value Health. 5:26-34.
235. Xu, J., C. Onyewu, H. J. Yoell, R. Y. Ali, R. J. Vilgalys, and T. G. Mitchell. 2001. Dynamic and heterogeneous mutations to fluconazole resistance in Cryptococcus neoformans. Antimicrob. Agents Chemother. 45:420-427.
236. Yamazumi, T., M. A. Pfaller, S. A. Messer, A. K. Houston, L. Boyken, R. J. Hollis, I. Furuta, and R. N. Jones. 2003. Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans. J. Clin. Microbiol. 41:267-272.
237. Yildiran, S. T., A. W. Fothergill, D. A. Sutton, and M. G. Rinaldi. 2002. In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592). Mycoses 45:378-383.
238. Yim, G., H. H. Wang, and J. Davies. 2007. Antibiotics as signalling molecules. Philos. Trans. R. Soc. Lond. B 362:1195-1200.
239. Young, J. C., I. Moarefi, and F. U. Hartl. 2001. Hsp90: a specialized but essential protein-folding tool. J. Cell Biol. 154:267-273.
240. Zaoutis, T. E., J. Argon, J. Chu, J. A. Berlin, T. J. Walsh, and C. Feudtner. 2005. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin. Infect. Dis. 41:1232-1239.
241. Zhao, C., U. S. Jung, P. Garrett-Engele, T. Roe, M. S. Cyert, and D. E. Levin. 1998. Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol. Cell. Biol. 18:1013-1022.
242. Zhao, R., and W. A. Houry. 2005. Hsp90: a chaperone for protein folding and gene regulation. Biochem. Cell Biol. 83:703-710.
243. Zhao, W., J. C. Panepinto, J. R. Fortwendel, L. Fox, B. G. Oliver, D. S. Askew, and J. C. Rhodes. 2006. Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence. Infect. Immun. 74:4865-4874.