Antifungals: Mechanism of action and resistance, established and novel drugs

Current Opinion in Microbiology

Volumn 1, Issue 5, 1998, Pages 547-557

  Georgopapadakou, Nafsika H ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ERGOSTEROL; PEPTIDE; PROTEIN SYNTHESIS INHIBITOR; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATASE; PYRROLE DERIVATIVE; SPHINGOLIPID;

ANTIBIOTIC RESISTANCE; BIOSYNTHESIS; DRUG ANTAGONISM; DRUG INDUSTRY; DRUG SCREENING; HUMAN; MYCOSIS; REVIEW;

ANTI-BACTERIAL AGENTS; ANTIBIOTICS, ANTIFUNGAL; ANTIFUNGAL AGENTS; AZOLES; DRUG EVALUATION; DRUG INDUSTRY; DRUG RESISTANCE, MICROBIAL; ERGOSTEROL; HUMANS; MYCOSES; PEPTIDES; PROTEIN SYNTHESIS INHIBITORS; PROTON-TRANSLOCATING ATPASES; SPHINGOLIPIDS;

EID: 0032173607     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1369-5274(98)80087-8     Document Type: Article

References (148)

1. Anaissie EJ: Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review. Clin Infect Dis 1992, 14:43-53.
2. Walsh TJ: Invasive fungal infections: problems and challenges in developing new antifungal compounds. In Emerging Targets in Antibacterial and Antifungal Chemotherapy. Edited by Sutcliffe J, Georgopapadakou NH. New York: Chapman and Hall; 1992:349-373.
3. Georgopapadakou NH, Walsh TJ: Human mycoses: drugs and targets for emerging pathogens. Science 1994, 264:371-373.
4. Beck-Sague CM, Jarvis WR: Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. J Infect Dis 1993, 167:1247-1251.
5. Nguyen MH, Peacock JE, Morris AJ, Tanner DC, Nguyen ML, Snydman DR, Wagener MM, Rinaldi MG, Yu VL: The changing face of candidemia - emergence of non-Candida albicans species and fungal resistance. Am J Med 1996, 100:617-623.
6. Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP: National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE program. Diagn Microbiol Infect Dis 1998, 31:327-332.
7. Panutti CS, Gingrich R, Pfaller MA, Kao C, Wenzel RP: Nosocomial pneumonia in patients having bone marrow transplant. Cancer 1992, 69:2653-2662.
8. Hughes WT: Pneumocystis carinii pneumonia: new approaches to diagnosis, treatment and prevention. Pediatr Infect Dis J 1991, 10:391-399.
9. Walsh TJ, Lyman CA, Pizzo PA: Laboratory diagnosis of invasive fungal infections in patients with neoplastic diseases. In Bailliere's Clinical Infectious Diseases International Practice and Research. Invasive Fungal Infections in Cancer Patients, vol 2. Edited by Meunier F. Philadelphia: Bailliere-Tidall; 1995:25-70.
10. Working Party of the British Society for Antimicrobial Chemotherapy: Therapy of deep fungal infection in haematological malignancy. J Antimicrob Chemother 1997, 40:779-788.
11. Fishman JA: The treatment of infection due to Pneumocystis carinii. Antimicrob Agents Chemother 1998, 42:1309-1314.
12. Roilides E, Walsh TJ, Rubin M, Venzon D, Pizzo PA: Effects of antifungal agents on the function of human neutrophils in vitro. Antimicrob Agents Chemother 1990, 34:196-201.
13. Martin E, Stuben A, Gorz A, Weller U, Bhakdi S: Novel aspect of amphotericin action: accumulation in human monocytes potentiates killing of phagocytosed Candida albicans. Antimicrob Agents Chemother 1994, 38:13-22.
14. Vago T, Baldi G, Colombo D, Barbareschi M, Norbiato G, Dallegri F, Bevilaqua M: Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes. Antimicrob Agents Chemother 1994, 38:2605-2611.
15. Johnson EM, Warnock DW, Richardson MD, Douglas CJ: In vitro effect of itraconazole, ketoconazole and amphotericin B on the phagocytic and candidacidal function of human neutrophils. J Antimicrob Chemother 1986, 18:83-92.
16. Vanden Bossche H, Marichal P, Odds FC: Molecular mechanisms of drug resistance in fungi. Trends Microbiol 1994, 2:393-400.
17. Graybill JR: Lipid formulations for amphotericin B: does the emperor need new clothes? Ann Int Med 1996, 124:921-923.
18. Hartse S, Bolard J: Amphotericin B: new life for an old drug. Trends Pharmac Sci 1996, 17:445-449.
19. Ibrahim AS, Mirbod F, Filler SG, Banno Y, Cole GT, Kitajima Y, Edwards JE, Nozawa EY, Ghannoum MA: Evidence implicating phospholipase as a virulence factor of Candida albicans. Infect Immun 1995, 63:1993-1998.
20. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto, Washington DC: American Society for Microbiology; 1997:161.
21. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:29.
22. Kelly SL, Lamb DC, Kelly DE, Manning NJ, Loeffer J, Einsele H: Resistance to fluconazole and amphotericin in Candida albicans from AIDS patients. Lancet 1996, 348:1523-1524.
23. 5,6 desaturation. FEBS Lett 1997, 400:80-82. This paper describes the basis for the cross-resistance between fluconazole and amphotericin observed in some clinical isolates.
24. Sokol-Anderson M, Sligh JE, Elberg S, Brajtburg J, Kobayashi GS, Medoff G: Role of cell defense against oxidative damage in the resistance of Candida albicans to the killing effect of amphotericin B. Antimicrob Agents Chemother 1988, 32:702-705.
25. Anaissie E, Nelson P, Beremand M, Kontoyiannis D, Rinaldi M: Fusarium-caused hyalohyphomycosis: an overview. Curr Top Med Mycol 1992, 4:231-249.
26. Walsh TJ, Melcher G, Rinaldi M, Lecciones J, McGough D, Lee J, Callender D, Rubin M, Pizzo PA: Trichosporon beigelii: an emerging pathogen resistant to amphotericin B. J Clin Microbiol 1990, 28:1616-1622.
27. Fromtling R: Overview of medically important azole derivatives. Clin Microbiol Rev 1988, 1:187-217.
28. Georgopapadakou NH, Walsh TJ: Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother 1996, 40:279-291.
29. Georgopapadakou NH, Dix BA, Smith SA, Freudenberger J Funke PT: Effect of antifungal agents on lipid biosynthesis and membrane integrity in Candida albicans. Antimicrob Agents Chemother 1987, 31:46-51.
30. Georgopapadakou NH, Bertasso A: Effects of ergosterol inhibitors on chitin synthesis in vitro and in vivo. In Recent Advances in Chemotherapy: Antimicrobial Section II. Proc Intl Congr Chemother. Edited by Adam A, Lode H, Rubinstein E. Munich: Futuramed Verlag; 1992:2208-2209.
31. Parks LW, Lorenz RT, Casey WM. Functions for sterols in yeast membranes. In Emerging Targets in Antibacterial and Antifungal Chemotherapy. Edited by Sutcliffe J. Georgopapadakou NH, New York: Chapman and Hall; 1992:393-409.
32. Shimokawa O, Nakayama H: Increased sensitivity of Candida albicans cells accumulating 14α-methylated sterols to active oxygen: possible relevance to in vivo efficacies of azole antifungal agents. Antimicrob Agents Chemother 1992, 36:1626-1629.
33. Johnson EM, Warnock DW, Luker J, Porter SR, Scully C: Emergence of azole drug resistance in Candida species from HIV-infected patients receiving prolonged fluconazole therapy for oral candidosis. J Antimicrob Chemother 1995, 35:103-114.
34. Rex HJ, Rinaldi MG, Pfaller MA: Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995, 39:1-8.
35. Coker RJ, Harris JRW: Failure of fluconazole treatment in cryptococcal meningitis despite adequate CSF levels. J Infect 1991, 23:101-103.
36. Kelly SL, Rowe J, Watson PF: Molecular genetic studies on the mode of action of azole antifungal agents. Biochem Soc Trans 1991, 19:796-798.
37. White TC, Marr KA, Bowden RA: Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 1998, 11:382-402. A thoughtful, up-to-date review of resistance mechanisms for major antifungal classes.
38. Hitchcock CA: Resistance of Candida albicans to azole antifungal agents. Biochem Soc Trans 1993, 21:1039-1047.
39. Sanglard D, Ischer F, Calabrese D, de Micheli M, Bille J: Multiple resistance mechanisms to azole antifungal agents in yeast clinical isolates. Drug Resist Updates 1998, 1:255-265. A superb review of mechanisms of clinical resistance to azole antifungals that incorporates some unpublished work from the authors' laboratory.
40. Kelly SL, Lamb DC, Corran AJ, Baldwin BC, Kelly DE: Mode of action and resistance to azole antifungals associated with the formation of 14α-methylergosta-8,24(28)-dien-3β,6α-diol. Biochem Biophys Res Commun 1995, 207:910-915.
41. Taglicht D, Michaelis S: Saccharomyces cerevisiae ABC proteins and their relevance to human health and disease. Methods Enzymol 1998, 292: in press.
42. Goffeau A, Park J, Paulsen IT, Jonniaux JL, Dinh T, Mordant P, Saier MH: Multidrug-resistant transport proteins in yeast: complete inventory and phylogenetrc characterization of yeast open reading frames within the major facilitator superfamily. Yeast 1997, 13:43-54.
43. Saccharomyces Genome Database on World Wide Web URL: http://genome-www.stanford.edu/Saccharomyces A very useful web site for the genome of this model, nonpathogenic yeast. It serves as a reference for less well studied genomes, such as Candida albicans, with which it shares some homology.
44. Prasad R, De WP, Goffeau A, Balzi E: Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr Genet 1997, 27:320-329.
45. 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. Microbiol 1997, 143:405-416.
46. Balan I, Alarco AM, Raymond M: The Candida albicans CDR3 gene codes for an opaque-phase ABC transporter. J Bacteriol 1997, 179:7210-7218.
47. Hernaez ML, Gil C, Pla J, Nombela C: Induced expression of the Candida albicans multidrug resistance gene CDR1 in response to fluconazole and other antifungals. Yeast 1998, 14:517-526. This is the first description of azole-induced expression of an efflux pump.
48. Sanglard D, Kuchler K, Ischer F, Pagani JL, Monod M, Bille J: Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother 1995, 39:2379-2386.
49. Ryder NS: Mechanism of action and biochemical selectivity of allylamine antimycotic agents. Ann NY Acad Sci 1988, 544:208-220.
50. Ryder NS: Squalene epoxidase as a target for the allylamines. Biochem Soc Trans 1991, 19:774-777.
51. Georgopapadakou NH, Bertasso A: Effects of squalene epoxidase inhibitors in Candida albicans. Antimicrob Agents Chemother 1992, 36:1779-1781.
52. Orth AB, Henry MJ, Sisler HD: Mechanism of resistance to terbinafine in two isolates of Ustilago maydis. Pestic Biochem Physiol 1990, 37:182-191.
53. Francis P, Walsh TJ: Evolving role of flucytosine in immunocompromised patients: new insights into safety, pharmacokinetics, and antifungal therapy. Rev Infect Dis 1992, 15:1003-1018.
54. Viviani MA: Flucytosine - what is its future? J Antimicrob Chemother 1995, 35:241-244.
55. Polak A: Mode of action studies. In Handbook of Experimental Pharmacology, vol 96. Chemotherapy of Fungal Diseases. Edited by Ryley JF. Heidelberg: Springer-Verlag; 1990:153-182.
56. Tkacz JS. Glucan biosynthesis in fungi and its inhibition. In Emerging Targets in Antibacterial and Antifungal Chemotherapy. Edited by Sutcliffe J, Georgopapadakou NH. New York: Chapman and Hall; 1992:495-523.
57. Douglas CM, Marrinan JA, Li W, Kurtz MB: A Saccharomyces cerevisiae mutant with echinocandin-resistant 1,3 - D-glucan synthase. J Bacteriol 1994, 176:5686-5696.
58. Bickle M, Delley P-A, Schmidt A, Hall MN: Cell wall integrity modulates RHO1 activity via the exchange factor ROM2. EMBO J 1998, 17:2235-2245.
59. Mol PC, Park H-M, Mullins JT, Cabib EA: GTP-binding protein regulates the activity of (1,3) - glucan synthase, an enzyme directly involved in yeast cell wall morphogenesis. J Biol Chem 1994, 269:31267-31274.
60. Drgonova J, Drgon T, Tanaka K, Kollar R, Chen G-C, Ford RA, Chan CSM, Takai Y, Cabib E: Rho1p, a yeast protein at the interface between cell polarization and morphogenesis. Science 1996, 272:277-279.
61. Qadota H, Python CP, Inoue SB, Arisawa M, Anraku Y, Zheng Y, Watanabe T, Levin DE, Ohya Y: Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3 - glucan synthase. Science 1996, 272:279-281.
62. Errede B, Levin DE: Yeast and signal transduction. Curr Opin Cell Biol 1993, 5:254-260.
63. Nonaka H, Tanaka K, Hirano H, Fujiwara T, Kohno H, M. Umikawa M, Mino A, Takai Y: A downstream target of RH01 small GTP-binding protein is PKC1, a homolog of protein kinase C, which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae. EMBO J 1995, 14:5931.
64. Levin DE, Bartlett-Heubusch E: Mutants in the Saccharomyces cerevisiae PKC1 gene display a cell cycle-specific osmotic instability defect. J Cell Biol 1992, 116:1221-1229.
65. Cid VJ, Duran A, Del Rey F, Snyder MP, Nombela C, Sanchez M: Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae. Microbiol Rev 1995, 59:345-386.
66. Douglas CM, Foor F, Marrinan JA, Morin N, Nielsen JB, Dahl AM, Mazur P, Baginsky W, Li WL, El Sherbeini M et al.: The Saccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3 - D-glucan synthase. Proc Natl Acad Sci USA 1994, 91:1207-1211.
67. Mazur P, Morin N, Baginsky W, El-Sherbeini M, Clemas JA, Nielsen JB, Poor F: Differential expression and function of two homologous subunits of yeast 1,3-β-D-glucan synthase. Mol Cell Biol 1995, 15:5671-5681.
68. Georgopapadakou NH, Tkacz JS: The fungal cell wall as a drug target. Trends Microbiol 1995, 3:98-104.
69. Gozalbo D, Elorza MV, Sanjuan R, Marcilla A, Valentin E, Sentandreu R: Critical steps in fungal cell wall synthesis: strategies for their inhibition. Pharmac Ther 1993, 60:337-345.
70. Debono N, Gordec RS: Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 1994, 48:471-497.
71. Current WL, Tang J, Boylan C, Watson P, Zeckner D, Turner W, Rodriguez M, Dixon C, Ma D, Radding JA: Glucan biosynthesis as a target for antifungals: the echinocandin class of antifungal agents. In Antifungal Agents: Discovery and Mode of Action. Edited by Dixon GK, Copping LG, Hollomon DW. Oxford: Bios Scientific Publishers; 1995:143-160.
72. Abruzzo GK, Flattery AM, Gill CJ, Kong L, Smith JG, Krupa D, Pikounis VB, Kropp H, Bartizal K: Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, L-731373 with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis. Antimicrob Agents Chemother 1995, 39:1077-1081.
73. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1996 Sept 15-18, New Orleans. Washington DC: American Society for Microbiology; 1996:104.
74. Denning DW: Echinocandins and pneumocandins - a new antifungal class with a novel mode of action. J Antimicrob Chemother 1997, 40:611-614. A readable review of this class of β-(1,3)-glucan synthase inhibitors, focusing on the two compounds that are currently in clinical development.
75. Radding JA, Heidler SA, Turner WW: Photoaffinity analog of the semisynthetic echinocandin LY303366: identification of echinocandin targets in Candida albicans. Antimicrob Agents Chemother 1998, 42:1137-1194. A surprising finding suggesting that echinocandins/pneumocandins may interact with proteins other than their target, β-(1,3)-glucan synthase.
76. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:186.
77. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:159.
78. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:160.
79. Georgopapadakou NH: Cell-wall active antifungals and emerging targets. In Antiinfectives: Recent Advances in Chemistry and Structure-Activity Relationships, Edited by Bentley PH, O-Hanlon PJ. Cambridge: The Royal Society of Chemistry; 1997:163-175. A useful summary of cell fungal cell wall biosynthesis and its inhibition.
80. Bulawa CE: Genetics and molecular biology of chitin synthesis in fungi. Annu Rev Microbiol 1993, 47:505-534.
81. Cabib E: Differential inhibition of chitin synthases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins. Antimicrob Agents Chemother 1991, 35:170-173.
82. Gaughran JP, Lai MH, Kirsch DR, Silverman SJ: Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo. J Bacteriol 1994, 176:5857-5860.
83. Bulawa CE, Miller DW, Henry LK, Becker JM: Attenuated virulence of chitin-deficient mutants of Candida albicans. Proc Natl Acad Sci USA 1995, 92:10570-10574.
84. Oki T, Kakushima M, Hirano M, Takahashi A, Ohta A, Masuyoshi S, Hatori M, Kamei H: In vitro and in vivo antifungal activities of BMS-181184. J Antibiot 1992, 45:1512-1517.
85. Fungtomc JC, Minassian B, Huczko E, Kolek B, Bonner DP, Kessler RE: In vitro antifungal and fungicidal spectra of a new pradimicin derivative, BMS-181184. Antimicrob Agents Chemother 1995, 39:295-300.
86. Ueki T, Numata K-I, Sawada Y, Nishio M, Ohkuma H, Toda S, Kamachi, Fukagawa Y, Oki T: Studies on the mode of antifungal action of pradimicin antibiotics. II. D-Mannopyranoside-binding site and calcium-binding site. J Antibiot 1993, 46:455-469.
87. Georgopapadakou NH: Antifungals targeted to the cell wall. Exp Opin Invest Drugs 1997, 6:147-150.
88. Oehlschlager AC, Czyzewska E: Rationally designed inhibitors for sterol biosynthesis. In Emerging Targets in Antibacterial and Antifungal Chemotherapy. Edited by Sutcliffe J, Georgopapadakou NH. New York: Chapman and Hall; 1992: 437-475.
89. Mercer El: Inhibitors of sterol biosynthesis and their applications. Prog Lipid Res 1993, 2:357-416.
90. Koltin Y, Hitchcock CA: The search for new triazole antifungal agents. Curr Opin Chem Biol 1997, 1:176-182.
91. Dodd DS, Oehlschlager AC, Georgopapadakou NH, Polak AM, Hartman PG: Synthesis of inhibitors of 2,3-oxidosqualene lanosterol cyclase. Part II: cyclocondensation of γ,δ-unsaturated β-ketoesters with imines. J Org Chem 1992, 57:7226-7234.
92. Zheng YF, Oehlschlager AC, Geargopapadakou NH, Hartman PG, Scheliga P. Synthesis of the sulfur- and sulfoxide-substituted 2,3-oxidosqualenes and their evaluation as inhibitors of 2,3-oxidosqualene-lanosterol cyclase. J Amer Chem Soc 1995, 117:670-680.
93. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington: American Society for Microbiology; 1997:162.
94. Dawson MJ, Farthing JE, Marshall PS, Middleton RF, O'Neill MJ, Shuttleworth A, Stylli C, Tait RM, Taylor PM, Wildman HG et al.: The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. I, Taxonomy, fermentation, isolation, physicochemical properties and biological activity. J Antibiot 1992, 45:639-647.
95. Robinson GW, Tsay YH, Kienzle BK, Smith-Monroy CA, Bishop RW: Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation. Mol Cell Biol 1993, 13:2706-2717.
96. Belfield GP, Tuite MF: Translation elongation factor 3: a fungus-specific translation factor? Mol Microbiol 1993, 8:411-418.
97. Ypma-Wong MF, Fonzi WA, Sypherd PS: Fungus-specific translation elongation factor 3 gene present in Pneumocystis carinii. Infect Immun 1992, 60:4140-4145.
98. Colthurst DR, Santos M, Grant CM, Tuite MF: Candida albicans and three other Candida species contain an elongation factor structurally and functionally analogous to elongation factor 3. FEMS Lett 1991, 80:45-50.
99. Belfield GP, Ross-Smith NJ, Tuite MF: Translation elongation factor 3 (EF-3): an evolving eukaryotic ribosomal protein? J Mol Evol 1995, 41:376-387.
100. Triana Alonso FJ, Chakraburtty K, Nierhaus KH: The elongation factor 3 unique in higher fungi and essential for protein biosynthesis is an E site factor. J Biol Chem 1995, 270:20473-20478.
101. Sarthy AV, McGonigal T, Capobianco JO, Schmidt M, Green SR, Moehle CM, Goldman RC: Identification and kinetic analysis of a functional homolog of elongation factor 3, YEF3 in Saccharomyces cerevisiae. Yeast 1998, 14:239-253. This paper brings up the possibility that there may be more than a single elongation factor 3 in fungi.
102. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:155.
103. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:155.
104. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:156.
105. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto. Washington DC: American Society for Microbiology; 1997:155.
106. th Interscience Conference Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sept 28-Oct 1; Toronto, Washington DC: American Society for Microbiology; 1997:155.
107. Kinsman OS, Chalk PA, Jackson HC, Middleton RF, Shuttleworth A, Rudd BAM, Jones CA, Noble HM, Wildman HG, Dawson MJ, Stylli C et al.: Isolation and characterization of an antifungal antibiotic (GR135402) with protein synthesis inhibition. J Antibiot 1998, 51:41-49.
108. Johnson DR, Bhatnagar RS, Knoll LJ, Gordon JI: Genetics and biochemical studies of protein N-myristoylation. Annu Rev Biochem 1994, 63:869-914.
109. Langner CA, Lodge JK, Travis SJ, Caldwell JE, Lu T, Li Q, Bryant ML, Devadas B, Gokel GW, Kobayashi GS, Gordon JI: 4-Oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I. J Biol Chem 1992, 267:17159-17169.
110. Lodge JK, Jackson-Machelski E, Toffaletti DL, Perfect JR, Gordon JI: Targeted gene replacement demonstrates that myristoylCoA:protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans. Proc Nat Acad Sci USA 1994, 91:12008-12012.
111. Weinberg RA, McWherter CA, Freeman SK, Wood DC, Gordon JI, Lee SC: Genetic studies reveal that myristoylCoA:protein N-myristoyltransferase is an essential enzyme in Candida albicans. Mol Microbiol 1995, 6:241-250.
112. Lodge JK, Johnson RL, Weinberg RA, Gordon JI. I. Comparison of myristoyl CoA:protein N-myristoyltransferases from three pathogenic fungi - Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans. J Biol Chem 1994, 269:2996-3009.
113. Kishore NS, Wood DC, Mehta PP, Wade AC, Liu T, Gokel GW, Gordon JI: A comparison of the acyl chain specificities of human myristoyl-CoA synthetase and human myristoyl-CoA protein N-myristoyltransferase. J Biol Chem 1993, 268:4889-4902.
114. Rocque WJ, McWherter CA, Wood DC, Gordon JI: A comparative analysis of the kinetic mechanism and peptide substrate specificity of human and Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase. J Biol Chem 1993, 268:9964-9971.
115. Weston SA, Camble R, Colls J, Rosenbrock G, Taylor I, Egerton M, Tucker AD, Tunnicliffe A, Mistry A, Mancia F et al.: Crystal structure of the anti-fungal target N-myristoyl transferase. Nat Struct Biol 1998, 5:213-221. This excellent paper on the crystal structure of N-myristoyl transferase will undoubtedly aid in rational drug design.
116. Devadas B, Freeman SK, Zupec ME, Lu HF, Nagarajan SR, Kishore NS, Lodge JK, Kuneman DW, McWherter CA, Vinjamoori DV et al.: Design and synthesis of novel imidazole-substituted dipeptide amides as potent and selective inhibitors of Candida albicans myristoylCoA:protein N-myristoyltransferase and identification of related tripeptide inhibitors with mechanism-based antifungal activity. J Med Chem 1997, 40:2609-2625.
117. Devadas B, Freeman SK, McWherter CA, Kishore NS, Lodge JK, Jackson-Machelski E, Gordon JI, Sikorski JA: Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N-myristoyltransferase. J Med Chem 1998, 41:996-1000. This latest report on N-myristoyltransferase inhibitors moves away from peptides and towards compounds with antifungal activity.
118. deNobel H, Lipke PN: Is there a role for GPIs in yeast cell-wall assembly? Trends Cell Biol 1994, 4:42-45.
119. Caro LHP, Tettelin H, Vossen JH, Ram AFJ, van den Ende H, Klis FM: In silicio identification of glycosyl phosphatidylinositol-anchored plasma membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 1997, 13:1477-1489. This interesting report suggests that the synthesis of glycosyl phosphatidylinositol-anchored proteins may be an antifungal target.
120. Lester RL, Dickson RC: Sphingolipids with inositolphosphate-containing head groups. Adv Lipid Res 1993, 26:253-273.
121. Merrill AH, Liotta DC, Riley RT: Fumonisins: fungal toxins that shed light on sphingolipid function. Trends Cell Biol 1996, 6:218-223.
122. Mandala S, Thornton R, Frommer B, Curotto J, Rozdilsky W, Kurtz M, Giacobbe R, Bills G, Cabello M, Martin I: The discovery of australifungin, a novel inhibitor of sphinganine N-acyltransferase from Sporormiella australis. Producing organism, fermentation, isolation, and biological activity. J Antibiot 1995, 48:349-356.
123. Nagiek MM, Nagiec EE, Baltisberger JA, Wells GB, Lester RL, Dickson RC: Sphingolipid synthesis as a target for antifungal drugs. J Biol Chem 1997, 272:9809-9817. This excellent paper links the aureobasidin-resistance gene with nositolphosphorylceramide synthase and describes an activity assay for the enzyme.
124. Heidler SA, Radding JA: The AUR1 gene in Saccharomyces cerevisiae encodes dominant resistance to the antifungal agent aureobasidin A (LY295337). Antimicrob Agents Chemother 1995, 39:2765-2769.
125. Ikai K, Takesako K, Shiomi K, Moriguchi M, Umeda Y, Yamamoto J, Kato I, Naganawa H: Structure of aureobasidin A. J Antibiot 1991, 44:925-933.
126. Mandala SM, Thornton RA, Rosenbach M, Milligan J, Garcia-Calvo M, Bull HG, Kurtz MB: Khafrefungin, a novel inhibitor of sphingolipid synthesis. J Biol Chem 1997, 272:32709-32714.
127. Achenbach H, Muhlenfeld A, Fauth U, Zahner H: The galbonolides: novel, powerful antifungal macrolides from Streptomyces galbus spp. Eurythermus. Ann NY Acad Sci 1988, 544:128-140.
128. Mandala SM, Thornton RA, Milligan J, Rosenbach M, Garcia Calvo M, Bull HG, Harris G, Abruzzo GK, Flattery AM, Gill CJ et al.: Rustmicin, a potent antifungal agent, inhibits sphingolipid synthesis at inositol phosphoceramide synthase. J Biol Chem 1998, 273:14942-14949. This paper identifies the target of the macrolide galbonolide/rustimicin as inositolphosphorylceramide synthase.
129. Iwasaki S: Antimitotic agents; chemistry and recognition of tubulin molecule. Med Res Rev 1993, 13:183-198.
130. Shen LL, Baranowski J, Fostel J, Montgomery DA, Lartey PA: DNA topoisomerases from pathogenic fungi: targets for the discovery of antifungal drugs. Antimicrob Agents Chemother 1992, 36:2778-2784.
131. Dykstra CC, McClernon DR, Elwell LP, Tidwell RR: Selective inhibition of topoisomerases from Pneumocystis carinii compared with that of topoisomerases from mammalian cells. Antimicrob Agents Chemother 1994, 38:1890-1898.
132. Fostel J, Montgomery D: Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase 1 from Candida albicans. Antimicrob Agents Chemother 1995, 39:586-592.
133. Rosowsky A, Hynes JB, Queener SF: Structure-activity and structure-selectivity studies on diaminoquinazolines and other inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase. Antimicrob Agents Chemother 1995, 39:79-86.
134. Perfect JR, Toffaletti DL, Rude TH: The gene encoding phosphoribosyl-aminoimidazole carboxylase (ADE2) is essential for growth of Cryptococcus neoformans in cerebrospinal fluid. Infect Immun 1993, 61:4446-4451.
135. Gustafson G, Davis G, Waldron C, Smith A, Henry M: Identification of a new antifungal target site through a dual biochemical and molecular-genetics approach. Curr Genet 1996, 30:159-165.
136. Chen SF, Perrella FW, Behrens DL, Papp LM: Inhibition of dihydroorotate dehydrogenase activity by brequinar sodium. Cancel Res 1992, 52:3521-3527.
137. Konishi M, Nishio M, Saitoh K, Miyaki T, Oki T, Kawaguchi H: Cispentacin, a new antifungal antibiotic. I. Production, isolation, physicochemical properties, and structure. J Antibiot 1989, 42:1749-1755.
138. Oki T, Hirano M, Tomatsu K, Numata K-I, Kamei H: Cispentacin, a new antifungal antibiotic. II. In vitro and in vivo antifungal activities. J Antibiot 1989; 42:1756-1760.
139. Capobianco JO, Zakula D, Coen ML, Goldman RC: Anticandidal activity of cispentacin. The active transport by amino acid permease and possible mechanisms of action. Biochem Biophys Res Commun 1993, 190:1037-1044.
140. Yamaki H, Yamaguchi M, Imamura H, Suzuki H, Nishimura T, Saito H, Yamaguchi H: The mechanism of antifungal action of (S)-2-amino-4-oxo-5-hydroxypentanoic acid, RI 331: the inhibition of homoserine dehydrogenase in Saccharomyces cerevisiae. Biochem Biophys Res Commun 1990, 168:837-843.
141. Aoki Y, Kondoh M, Nakamura M, Fujii T, Yamazaki T, Shimada H, Arisawa M: A new methionine antagonist that has antifungal activity: mode of action. J Antibiot 1994, 47:909-916.
142. McCann PP, Pegg AE: Ornithine decarboxylase as an enzyme target for therapy. Pharmac Ther 1992, 54:195-215.
143. Saric M, Clarkson AB Jr: Ornithine decarboxylase in Pneumocystis carinii and implications for therapy. Antimicrob Agents Chemother 1994, 38:2545-2552.
144. Monk BC, Perlin DS: Fungal plasma membrane protein pumps as promising new antifungal targets. Crit Rev Microbiol 1994, 20:209-223.
145. Ben-Yaacov R, Becker JM, Oppenheim JM, Oppenheim A, Goldway M, Schmidt R, Jiang W, Clifford J, Koltin Y: Multidrug resistance in Candida albicans. J Cell Biochem 1995, B4:146.
146. Balzi E, Goffeau A: Genetics and biochemistry of yeast multidrug resistance. Biochim Biophys Acta 1994, 1187:152-162.
147. Groll AH, De Lucca AJ, Walch TJ: Emerging targets for the development of novel antifungal therapeutics. Trends Microbiol 1998, 6:117-124. This is an excellent minireview on antifungal drugs currently in development and targets under investigation.
148. Masubuchi M, Okuda T, Shimada H: Antifungal agent, its preparation and microorganism there for. European patent application, April/21/1993, EP 0537622A.