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Chapter 1 : Fungal Molecular Pathogenesis: What Can It Do and Why Do We Need It?

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Fungal Molecular Pathogenesis: What Can It Do and Why Do We Need It?, Page 1 of 2

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Abstract:

As molecular studies are applied to study the pathogenesis of invasive mycoses, it is essential that the parameters of the host-parasite interactions are known. The issue of clinical antifungal drug resistance and the impact of molecular studies on these invasive mycoses can be discussed under several categories: (i) diagnosis, (ii) immunomodulation, (iii) drug prescription, (iv) surgery, (v) prevention, (vi) new antifungal agents, and (vii) drug combinations. This chapter talks about how molecular studies of medically relevant fungi have begun to find uses in the clinical arena and discusses their potential to make a major impact on the outcome of human mycoses. There are two major issues in clinical diagnosis in which molecular biology is likely to lead to significant advances. First, despite the availability of several new diagnostic tests for invasive candidiasis and aspergillosis, there remain, from a clinical standpoint, opportunities to make an earlier specific fungal diagnosis or prevent the use of empirical antifungal therapies. The second area in which molecular biology is poised to make a major diagnostic contribution in the clinical mycology laboratory is in strain or isolate identification. The use of antifungal combinations to treat invasive mycoses has been a controversial topic because there are few evidence-based studies that support their widespread clinical use. In today's environment of constant fungal threat, it is both exciting and helpful that fungal molecular pathogenesis is maturing into a science with practical applications.

Citation: Perfect J, Casadevall A. 2006. Fungal Molecular Pathogenesis: What Can It Do and Why Do We Need It?, p 3-11. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch1

Key Concept Ranking

Fungal Pathogenesis
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Antifungal Agents
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Fungal Infections
0.53784466
Magnetic Resonance Imaging
0.42378256
Chronic Granulomatous Disease
0.4138115
Clinical Research
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References

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1. 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. 43:214222.
2. Bellocchio, S.,, R. Gaziano,, S. Bozza,, G. Rossi,, C. Montagnoli,, K. Perruccio,, M. Calvitti,, L. Pitzurra, and, L. Romani. 2005. Liposomal amphotericin B activates antifungal resistance with reduced toxicity by diverting Toll-like receptor signalling from TLR-2 to TLR-4. J. Antimicrob. Chemother. 55:214222.
3. Biondo, C.,, C. Beninati,, D. Delfino,, M. Oggioni,, G. Mancuso,, A. Midiri,, M. Bombaci,, G. Tomaselli, and, G. Teti. 2002. Identification and cloning of a cryptococcal deacetylase that produces protective immune responses. Infect. Immun. 70:23832391.
4. Borges, C. L.,, M. Pereira,, M. S. Felipe,, F. P. de Faria,, F. J. Gomez,, G. S. Deepe,, Jr., and, C. M. Soares. 2005. The antigenic and catalytically active formamidase of Paracoccidioides brasiliensis: protein characterization, cDNA and gene cloning, heterologous expression and functional analysis of the recombinant protein. Microbes Infect. 7:6677.
5. Brakhage, A. A., and K. Langfelder. 2002. Menacing mold: the molecular biology of Aspergillus fumigatus. Annu. Rev. Microbiol. 56:433455.
6. Brouwer, A. E.,, A. Rajanuwong,, W. Chierakul,, G. E. Griffin,, R. A. Larsen,, N. J. White, and, T. S. Harrison. 2004. Combination antifungal therapies for HIV-associated cryptococcal meningitis: feasibility and power of quantitative CSF cultures to determine fungicidal activity. Lancet 363:17641767.
7. Casadevall, A. 1999. Passive antibody therapies: progress and continuing challenges. Clin. Immunol. 93:515.
8. Casadevall, A., and, L. A. Pirofski. 2003. The damage-response framework of microbial pathogenesis. Nat. Rev. Microbiol. 1:1724.
9. Choi, E. H.,, C. B. Foster,, J. G. Taylor,, H. C. Erichsen,, R. A. Chen,, T. J. Walsh,, V. J. Anttila,, T. Ruutu,, A. Palotie, and, S. J. Chanock. 2003. Association between chronic disseminated candidiasis in adult acute leukemia and common IL4 promoter haplotypes. J. Infect. Dis. 187:11531156.
10. Clark, T. A.,, S. A. Slavinski,, J. Morgan,, T. Lott,, B. A. Arthington-Skaggs,, M. E. Brandt,, R. M. Webb,, M. Currier,, R. H. Flowers,, S. K. Fridkin, and, R. A. Hajjeh. 2004. Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital. J. Clin. Microbiol. 42:44684472.
11. Cole, G. T.,, J. M. Xue,, C. N. Okeke,, E. J. Tarcha,, V. Basrur,, R. A. Schaller,, R. A. Herr,, J. J. Yu, and, C. Y. Hung. 2004. A vaccine against coccidioidomycosis is justified and attainable. Med. Mycol. 42:189216.
12. Cox, G. M.,, H. C. McDade,, S. C. Chen,, S. C. Tucker,, M. Gottfredsson,, L. C. Wright,, T. C. Sorrell,, S. D. Leidich,, A. Casadevall,, M. A. Ghannoum, and, J. R. Perfect. 2001. Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans. Mol. Microbiol. 39:166175.
13. 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. 21:546559.
14. de Aguirre, L.,, S. F. Hurst,, J. S. Choi,, J. H. Shin,, H. P. Hinrikson, and, C. J. Morrison. 2004. Rapid differentiation of Aspergillus species from other medically important opportunistic molds and yeasts by PCR-enzyme immunoassay. J. Clin. Microbiol. 42:34953504.
15. Deepe, G. S., Jr., and, R. S. Gibbons. 2002. Cellular and molecular regulation of vaccination with heat shock protein 60 from Histoplasma capsulatum. Infect. Immun. 70:37593767.
16. Devi, S. J. N. 1996. Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. Vaccine 14:841842.
17. Diehn, M., and, D. A. Relman. 2001. Comparing functional genomic datasets: lessons from DNA microarray analyses of host-pathogen interactions. Curr. Opin. Microbiol. 4:95101.
18. Diekema, D. J., and, M. A. Pfaller. 2004. Nosocomial candidemia: an ounce of prevention is better than a pound of cure. Infect. Control Hosp. Epidemiol. 25:624626.
19. Fierer, J.,, L. Walls,, F. Wright, and, T. N. Kirkland. 1999. Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice. Infect. Immun. 67:29162919.
20. Ganendren, R.,, F. Widmer,, V. Singhal,, C. Wilson,, T. Sorrell, and, L. Wright. 2004. In vitro antifungal activities of inhibitors of phospholipases from the fungal pathogen Cryptococcus neoformans. Antimicrob. Agents Chemother. 48:15611569.
21. Gudlaugsson, O.,, S. Gillespie,, K. Lee,, B. J. Vande,, J. Hu,, S. Messer,, L. Herwaldt,, M. Pfaller, and, D. Diekema. 2003. Attributable mortality of nosocomial candidemia, revisited. Clin. Infect. Dis. 37:11721177.
22. Gutzmer, R.,, S. Mommert,, U. Kuttler,, T. Werfel, and, A. Kapp. 2004. Rapid identification and differentiation of fungal DNA in dermatological specimens by LightCycler PCR. J. Med. Microbiol. 53:12071214.
23. Huang, Y. C.,, L. H. Su,, T. L. Wu, and, T. Y. Lin. 2004. Genotyping analysis of colonizing candidal isolates from very-low-birthweight infants in a neonatal intensive care unit. J. Hosp. Infect. 58:200203.
24. Hwang, L.,, D. Hocking-Murray,, A. K. Bahrami,, M. Andersson,, J. Rine, and, A. Sil. 2003. Identifying phase-specific genes in the fungal pathogen Histoplasma capsulatum using a genomic shotgun microarray. Mol. Biol. Cell 14:23142326.
25. Ibrahim, A. S.,, B. J. Spellberg,, V. Avenissian,, Y. Fu,, S. G. Filler, and, J. E. Edwards, Jr. 2005. Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect. Immun. 73:9991005.
26. Ikeda, Y.,, K. Umemura,, K. Kondo,, K. Sekiguchi,, S. Miyoshi, and, M. Nakashima. 2004. Pharmacokinetics of voriconazole and cytochrome P450 2C19 genetic status. Clin. Pharmacol. Ther. 75:587588.
27. Johnson, M. D.,, C. MacDougall,, L. Ostrosky-Zeichner,, J. R. Perfect, and, J. H. Rex. 2004. Combination antifungal therapy. Antimicrob. Agents Chemother. 48:693715.
28. Jones, T.,, N. A. Federspiel,, H. Chibana,, J. Dungan,, S. Kalman,, B. B. Magee,, G. Newport,, Y. R. Thorstenson,, N. Agabian,, P. T. Magee,, R. W. Davis, and, S. Scherer. 2004. The diploid genome sequence of Candida albicans. Proc. Natl. Acad. Sci. USA 101:73297334.
29. Jordanides, N. E.,, E. K. Allan,, L. A. McLintock,, M. Copland,, M. Devaney,, K. Stewart,, A. N. Parker,, P. R. Johnson,, T. L. Holyoake, and, B. L. Jones. 2005. A prospective study of real-time panfungal PCR for the early diagnosis of invasive fungal infection in haemato-oncology patients. Bone Marrow Transplant. 35:389395.
30. Kaur, R.,, I. Castano, and, B. P. Cormack. 2004. Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Antimicrob. Agents Chemother. 48:16001613.
31. Larriba, G.,, J. J. Rubio Coque,, A. Ciudad, and, E. Andaluz. 2000. Candida albicans molecular biology reaches its maturity. Int. Microbiol. 3:247252.
32. Larsen, R. A.,, P. G. Pappas,, J. Perfect,, J. A. Aberg,, A. Casadevall,, G. A. Cloud,, R. James,, S. Filler, and, W. E. Dismukes. 2005. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob. Agents Chemother. 49:952958.
33. Levitz, S. M.,, S. Nong,, M. K. Mansour,, C. Huang, and, C. Specht. 2001. Molecular characterization of a manno-protein with homology to chitin deacetylases that stimulates T-cell responses to Cryptococcus neoformans. Proc. Natl. Acad. Sci. USA 98:1042210427.
34. Loftus, B. J.,, E. Fung,, P. Roncaglia,, D. Rowley,, P. Amedeo,, D. Bruno,, J. Vamathevan,, M. Miranda,, I. J. Anderson,, J. A. Fraser,, J. E. Allen,, I. E. Bosdet,, M. R. Brent,, R. Chiu,, T. L. Doering,, M. J. Donlin,, C. A. D’Souza,, D. S. Fox,, V. Grinberg,, J. Fu,, M. Fukushima,, B. J. Haas,, J. C. Huang,, G. Janbon,, S. J. Jones,, H. L. Koo,, M. I. Krzywinski,, J. K. Kwon-Chung,, K. B. Lengeler,, R. Maiti,, M. A. Marra,, R. E. Marra,, C. A. Mathewson,, T. G. Mitchell,, M. Pertea,, F. R. Riggs,, S. L. Salzberg,, J. E. Schein,, A. Shvartsbeyn,, H. Shin,, M. Shumway,, C. A. Specht,, B. B. Suh,, A. Tenney,, T. R. Utterback,, B. L. Wickes,, J. R. Wortman,, N. H. Wye,, J. W. Kronstad,, J. K. Lodge,, J. Heitman,, R. W. Davis,, C. M. Fraser, and, R. W. Hyman. 2005. The genome of the basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science 307:13211324.
35. Lorenz, M. C.,, J. A. Bender, and, G. R. Fink. 2004. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot. Cell 3:10761087.
36. Magee, P. T.,, C. Gale,, J. Berman, and, D. Davis. 2003. Molecular genetic and genomic approaches to the study of medically important fungi. Infect. Immun. 71:22992309.
37. Mandel, M. A.,, G. G. Grace,, K. I. Osborn,, F. Schafer,, J. W. Murphy,, M. J. Orbach, and, J. N. Galgiani. 2002. The Cryptococcus neoformans gene DHA1 encodes an antigen that elicits a delayed-type hypersensitivity reaction in immune mice. Infect. Immun. 68:61966201.
38. 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. 44:23732381.
39. 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. 48:38713876.
40. 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. 47:22082216.
41. Mukherjee, P. K.,, K. R. Seshan,, S. D. Leidich,, J. Chandra,, G. T. Cole, and, M. A. Ghannoum. 2001. Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo. Microbiology 147:25852597.
42. Musher, B.,, D. Fredricks,, W. Leisenring,, S. A. Balajee,, C. Smith, and, K. A. Marr. 2004. Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J. Clin. Microbiol. 42:55175522.
43. Nemunaitis, J.,, J. D. Meyers,, C. D. Buckner,, K. Shannondorcy,, H. Shulman,, J. A. Bianco,, C. S. Higano,, E. Groves,, R. Storb,, J. Hansen,, F. R. Applebaum, and, J. W. Singer. 1991. Phase I trial of recombinant human macrophage colony-stimulating factor in patients with invasive fungal infections. Blood 78:907913.
44. Nosanchuk, J. D.,, R. Ovalle, and, A. Casadevall. 2001. Glyphosate inhibits melanization of Cryptococcus neofor-mans and prolongs survival of mice after systemic infection. J. Infect. Dis. 183:10931099.
45. Pappas, P. G.,, B. Bustamante,, E. Ticona,, R. J. Hamill,, P. C. Johnson,, A. Reboli,, J. Aberg,, R. Hasbun, and, H. H. Hsu. 2004. Recombinant interferon-gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis. J. Infect. Dis. 189:21852191.
46. Perfect, J. R.,, K. A. Wright, and, R. F. Hector. 1993. Synergistic interaction of nikkomycin and cilofungin against diverse fungi, p. 369–380. In H. Yamaguchi, G. S. Kobayashi, and H. Takahashi (ed.), Recent Progress in Antifungal Chemotherapy. Marcel Dekker, Inc., New York, N.Y.
47. Perfect, J. R. 1996. Fungal virulence genes as targets for antifungal chemotherapy. Antimicrob. Agents Chemother. 40:15771583.
48. Perfect, J. R.,, G. M. Cox,, J. Y. Lee,, C. A. Kauffman,, L. de Repentigny,, S. W. Chapman,, V. A. Morrison,, P. Pappas,, J. W. Hiemenz, and, D. A. Stevens. 2001. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin. Infect. Dis. 33:18241833.
49. 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. 42:44194431.
50. Polzehl, D.,, M. Weschta,, A. Podbielski,, H. Riechelmann, and, D. Rimek. 2005. Fungus culture and PCR in nasal lavage samples of patients with chronic rhinosinusitis. J. Med. Microbiol. 54:3137.
51. Rogers, P. D.,, M. M. Pearson,, J. D. Cleary,, D. C. Sullivan, and, S. W. Chapman. 2002. Differential expression of genes encoding immunomodulatory proteins in response to amphotericin B in human mononuclear cells identified by cDNA microarray analysis. J. Antimicrob. Chemother. 50:811817.
52. Schroder, N. W., and, R. R. Schumann. 2005. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect. Dis. 5:156164.
53. Silva Ferreira, M. E.,, J. L. Capellaro,, M. E. dos Reis,, 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. 48:44054413.
54. Stoll, M., and, R. E. Schmidt. 2004. Adverse events of desirable gain in immunocompetence: the immune restoration inflammatory syndromes. Autoimmun. Rev. 3:243249.
55. van der Horst, C. M.,, M. S. Saag,, G. A. Cloud, and National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. 1997. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N. Engl. J. Med. 337:1521.
56. White, T. C.,, S. Holleman,, F. Dy,, L. F. Mirels, and, D. A. Stevens. 2002. Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob. Agents Chemother. 46:17041713.
57. Winston, D. J.,, C. Emmanouilides,, K. Bartoni,, G. J. Schiller,, R. Paquette, and, M. C. Territo. 2004. Elimination of Aspergillus infection in allogeneic stem cell transplant recipients with long-term itraconazole prophylaxis: prevention is better than treatment. Blood 104:1581.
58. Wuthrich, M.,, H. I. Filutowicz,, T. Warner, and, B. S. Klein. 2002. Requisite elements in vaccine immunity to Blastomyces dermatitidis : plasticity uncovers vaccine potential in immune-deficient hosts. J. Immunol. 169:69696976.
59. Xie, H. G.,, R. B. Kim,, A. J. Wood, and, C. M. Stein. 2001. Molecular basis of ethnic differences in drug disposition and response. Annu. Rev. Pharmacol. Toxicol. 41:815850.
60. Yoo, J. H.,, J. H. Choi,, S. M. Choi,, D. G. Lee,, W. S. Shin,, W. S. Min, and, C. C. Kim. 2005. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematologic diseases. Clin. Infect. Dis. 40:392398.

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