Animal models in mycology: What have we learned over the past 30 years

Current Fungal Infection Reports

Volumn 7, Issue 1, 2013, Pages 68-78

  Kirkpatrick, William R ^a,b   Wiederhold, Nathan P ^a,c   Najvar, Laura K ^a,b   Patterson, Thomas F ^a,b  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

^c UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

Animal models; Antifungal therapy; Antifungal vaccines; Fungal diagnostics; Guinea pig; Host response; Mouse; Pathogenesis; Rabbit; Rat; Virulence

Indexed keywords

AMPHOTERICIN; AMPHOTERICIN B; ANIDULAFUNGIN; ANTIBIOTIC AGENT; CASPOFUNGIN; CHEMOKINE RECEPTOR CCR1; CORTICOSTEROID; ECHINOCANDIN; GLIOTOXIN; IMMUNOSUPPRESSIVE AGENT; ISAVUCONAZOLE; VIRULENCE FACTOR;

ANIMAL HOUSING; ANIMAL MODEL; ANIMAL WELFARE; ANTIBIOTIC THERAPY; ANTIFUNGAL ACTIVITY; ARTICLE; ASPERGILLOSIS; BIOFILM; BLOOD SAMPLING; CONIDIUM; CRYPTOCOCCOSIS; CRYPTOCOCCUS; DROSOPHILA MELANOGASTER; DRUG MEGADOSE; FUNGAL VIRULENCE; FUSARIOSIS; GALLERIA MELLONELLA; IMMUNE DEFICIENCY; IMMUNE STATUS; IMMUNOCOMPROMISED PATIENT; IMMUNOSUPPRESSIVE TREATMENT; INOCULATION; INVASIVE ASPERGILLOSIS; INVASIVE CANDIDIASIS; INVERTEBRATE; LUNG ASPERGILLOSIS; MENINGOENCEPHALITIS; MINIMUM INHIBITORY CONCENTRATION; MUCOCUTANEOUS CANDIDIASIS; MUCORMYCOSIS; MYCOLOGY; NEUTROPHIL; NONHUMAN; OROPHARYNX CANDIDIASIS; OVARIECTOMY; PATHOGENESIS; PNEUMOCYSTOSIS; PROGNOSIS; PSEUDALLESCHERIASIS; PULMONARY CRYPTOCOCCOSIS; STOMATITIS; THRUSH; VAGINA CANDIDIASIS;

EID: 84873721002     PISSN: 19363761     EISSN: 1936377X     Source Type: Journal    
DOI: 10.1007/s12281-012-0126-6     Document Type: Article

References (125)

1. • Capilla J, Clemons KV, Stevens DA. Animal models: an important tool in mycology. Med Mycol. 2007;45:657-84. A comprehensive review of animal models of invasive fungal infections.
2. Szabo EK, MacCallum DM. The contribution of mouse models to our understanding of systemic candidiasis. FEMS Microbiol Lett. 2011;320:1-8.
3. Naglik JR, Fidel Jr PL, Odds FC. Animal models of mucosal Candida infection. FEMS Microbiol Lett. 2008;283:129-39.
4. Upton A, Kirby KA, Carpenter P, et al. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44:531-40.
5. Marr KA, Carter RA, Boeckh M, et al. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100:4358-66.
6. Dixon DM, Polak A, Walsh TJ. Fungus dose-dependent primary pulmonary aspergillosis in immunosuppressed mice. Infect Immun. 1989;57:1452-6.
7. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362:1828-38.
8. Lewis RE, Kontoyiannis DP. Invasive aspergillosis in glucocorticoid- treated patients. Med Mycol. 2009;47 Suppl 1:S271-81.
9. Ng TT, Robson GD, Denning DW. Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology. 1994;140(Pt 9):2475-9.
10. •• Balloy V, Huerre M, Latge JP, Chignard M. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect Immun. 2005;73:494-503. Study comparing the pathogenesis of invasive pulmonary aspergillosis in neutropenic mice versus those who were immunosuppressed with corticosteroids alone.
11. • Spikes S, Xu R, Nguyen CK, et al. Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence. J Infect Dis. 2008;197:479-86. Study demonstrating differences in virulence for the mycotoxin gliotoxin between neutropenic and non-neutropenic immunosuppressed mice.
12. Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis. Antimicrob Agents Chemother. 2000;44:780-2.
13. Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of posaconazole in a rabbit model of invasive aspergillosis. Antimicrob Agents Chemother. 2000;44:780-2.
14. Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis. Antimicrob Agents Chemother. 2000;44:2865-8.
15. Mavridou E, Bruggemann RJ, Melchers WJ, et al. Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene. Antimicrob Agents Chemother. 2010;54:860-5.
16. Mavridou E, Bruggemann RJ, Melchers WJ, et al. Impact of cyp51A mutations on the pharmacokinetic and pharmacodynamic properties of voriconazole in a murine model of disseminated aspergillosis. Antimicrob Agents Chemother. 2010;54:4758-64.
17. Lewis RE, Wiederhold NP. Murine model of invasive aspergillosis. Methods Mol Med. 2005;118:129-42.
18. Wiederhold NP, Kontoyiannis DP, Chi J, et al. Pharmacodynamics of caspofungin in a murine model of invasive pulmonary aspergillosis: evidence of concentration-dependent activity. J Infect Dis. 2004;190:1464-71.
19. •• Sheppard DC, Rieg G, Chiang LY, et al. Novel inhalational murine model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2004;48:1908-11. First study to report the use of a nebulizer and an acrylic chamber for the aerosolization of Aspergillus conidia in order to establish invasive pulmonary aspergillosis in mice.
20. Sheppard DC, Graybill JR, Najvar LK, et al. Standardization of an experimental murine model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2006;50:3501-3.
21. Vallor AC, Kirkpatrick WR, Najvar LK, et al. Assessment of Aspergillus fumigatus burden in pulmonary tissue of guinea pigs by quantitative PCR, galactomannan enzyme immunoassay, and quantitative culture. Antimicrob Agents Chemother. 2008;52:2593-8.
22. Wiederhold NP, Thornton CR, Najvar LK, et al. Comparison of lateral flow technology and galactomannan and (1->3)-beta-D-glucan assays for detection of invasive pulmonary aspergillosis. Clin Vaccine Immunol. 2009;16:1844-6.
23. Lengerova M, Kocmanova I, Racil Z, et al. Detection and measurement of fungal burden in a guinea pig model of invasive pulmonary aspergillosis by novel quantitative nested real-time PCR compared with galactomannan and (1,3)-beta-D-glucan detection. J Clin Microbiol. 2012;50:602-8.
24. Dufresne SF, Datta K, Li X, et al. Detection of urinary excreted fungal galactomannan-like antigens for diagnosis of invasive aspergillosis. PLoS One. 2012;7:e42736.
25. Petraitis V, Petraitiene R, Hope WW, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: in vitro and in vivo correlations of the concentration- and dose- dependent interactions between anidulafungin and voriconazole by Bliss independence drug interaction analysis. Antimicrob Agents Chemother. 2009;53:2382-91.
26. Hope WW, Petraitis V, Petraitiene R, et al. The initial 96 hours of invasive pulmonary aspergillosis: histopathology, comparative kinetics of galactomannan and (1->3) beta-d-glucan and consequences of delayed antifungal therapy. Antimicrob Agents Chemother. 2010;54:4879-86.
27. Walsh TJ, Garrett K, Feuerstein E, et al. Therapeutic monitoring of experimental invasive pulmonary aspergillosis by ultrafast computerized tomography, a novel, noninvasive method for measuring responses to antifungal therapy. Antimicrob Agents Chemother. 1995;39:1065-9.
28. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. Antimicrob Agents Chemother. 2001;45:857-69.
29. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia. Antimicrob Agents Chemother. 2002;46:12-23.
30. Petraitis V, Petraitiene R, Groll AH, et al. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2002;46:1857-69.
31. Ho DY, Lee JD, Rosso F, Montoya JG. Treating disseminated fusariosis: amphotericin B, voriconazole or both? Mycoses. 2007;50:227-31.
32. Cortez KJ, Roilides E, Quiroz-Telles F, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008;21:157-97.
33. Lozano-Chiu M, Arikan S, Paetznick VL, et al. Treatment of murine fusariosis with SCH 56592. Antimicrob Agents Chemother. 1999;43:589-91.
34. Wiederhold NP, Najvar LK, Bocanegra R, et al. Efficacy of posaconazole as treatment and prophylaxis against Fusarium solani. Antimicrob Agents Chemother. 2010;54:1055-9.
35. Ruiz-Cendoya M, Marine M, Guarro J. Combined therapy in treatment of murine infection by Fusarium solani. J Antimicrob Chemother. 2008;62:543-6.
36. Spellberg B, Schwartz J, Fu Y, et al. Comparison of antifungal treatments for murine fusariosis. J Antimicrob Chemother. 2006;58:973-9.
37. Capilla J, Mayayo E, Serena C, et al. A novel murine model of cerebral scedosporiosis: lack of efficacy of amphotericin B. J Antimicrob Chemother. 2004;54:1092-5.
38. Rodriguez MM, Calvo E, Serena C, et al. Effects of double and triple combinations of antifungal drugs in a murine model of disseminated infection by Scedosporium prolificans. Antimicrob Agents Chemother. 2009;53:2153-5.
39. Rodriguez MM, Pastor FJ, Salas V, et al. Experimental murine scedosporiosis: histopathology and azole treatment. Antimicrob Agents Chemother. 2010;54:3980-4.
40. Gonzalez GM, Tijerina R, Najvar LK, et al. Activity of posaconazole against Pseudallescheria boydii: in vitro and in vivo assays. Antimicrob Agents Chemother. 2003;47:1436-8.
41. Harun A, Serena C, Gilgado F, et al. Scedosporium aurantiacum is as virulent as S. prolificans, and shows strain-specific virulence differences, in a mouse model. Med Mycol. 2010;48 Suppl 1:S45-51.
42. Ibrahim AS, Avanessian V, Spellberg B, Edwards Jr JE. Liposomal amphotericin B, and not amphotericin B deoxycholate, improves survival of diabetic mice infected with Rhizopus oryzae. Antimicrob Agents Chemother. 2003;47:3343-4.
43. Ibrahim AS, Bowman JC, Avanessian V, et al. Caspofungin inhibits Rhizopus oryzae 1,3-beta-D-glucan synthase, lowers burden in brain measured by quantitative PCR, and improves survival at a low but not a high dose during murine disseminated zygomycosis. Antimicrob Agents Chemother. 2005;49:721-7.
44. Ibrahim AS, Edwards Jr JE, Fu Y, Spellberg B. Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother. 2006;58:1070-3.
45. Rodriguez MM, Pastor FJ, Calvo E, et al. Correlation of in vitro activity, serum levels, and in vivo efficacy of posaconazole against Rhizopus microsporus in a murine disseminated infection. Antimicrob Agents Chemother. 2009;53:5022-5.
46. Rodriguez MM, Pastor FJ, Sutton DA, et al. Correlation between in vitro activity of posaconazole and in vivo efficacy against Rhizopus oryzae infection in mice. Antimicrob Agents Chemother. 2010;54:1665-9.
47. Rodriguez MM, Serena C, Marine M, et al. Posaconazole combined with amphotericin B, an effective therapy for a murine disseminated infection caused by Rhizopus oryzae. Antimicrob Agents Chemother. 2008;52:3786-8.
48. Ibrahim AS, Gebermariam T, Fu Y, et al. The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest. 2007;117:2649-57.
49. Liu M, Spellberg B, Phan QT, et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest. 2010;120:1914-24.
50. Lewis RE, Albert ND, Liao G, et al. Comparative pharmacodynamics of amphotericin B lipid complex and liposomal amphotericin B in a murine model of pulmonary mucormycosis. Antimicrob Agents Chemother. 2010;54:1298-304.
51. Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47:364-71.
52. Ibrahim AS, Gebremariam T, Husseiny MI, et al. Comparison of lipid amphotericin B preparations in treating murine zygomycosis. Antimicrob Agents Chemother. 2008;52:1573-6.
53. MacCallum DM, Odds FC. Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice. Mycoses. 2005;48:151-61.
54. • Lionakis MS, Lim JK, Lee CC, Murphy PM. Organ-specific innate immune responses in a mouse model of invasive candidiasis. J Innate Immun. 2011;3:180-99. Recent murine model that demonstrated differences in the temporal and spatial accumulation of leukocytes within different organs following intravenous challenge of mice with C. albicans.
55. Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011;10:168-73.
56. Liu Y, Mittal R, Solis NV, et al. Mechanisms of Candida albicans trafficking to the brain. PLoS Pathog. 2011;7:e1002305.
57. Hope WW, Mickiene D, Petraitis V, et al. The pharmacokinetics and pharmacodynamics of micafungin in experimental hematogenous Candida meningoencephalitis: implications for echinocandin therapy in neonates. J Infect Dis. 2008;197:163-71.
58. Petraitiene R, Petraitis V, Hope WW, et al. Cerebrospinal fluid and plasma (1->3)-beta-D-glucan as surrogate markers for detection and monitoring of therapeutic response in experimental hematogenous Candida meningoencephalitis. Antimicrob Agents Chemother. 2008;52:4121-9.
59. Spellberg B, Ibrahim AS, Edwards Jr JE, Filler SG. Mice with disseminated candidiasis die of progressive sepsis. J Infect Dis. 2005;192:336-43.
60. Lionakis MS, Fischer BG, Lim JK, et al. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLoS Pathog. 2012;8:e1002865.
61. Ostrosky-Zeichner L, Paetznick VL, Rodriguez J, et al. Activity of anidulafungin in a murine model of Candida krusei infection: evaluation of mortality and disease burden by quantitative tissue cultures and measurement of serum (1,3)-beta-D-glucan levels. Antimicrob Agents Chemother. 2009;53:1639-41.
62. Salas V, Pastor FJ, Calvo E, et al. Anidulafungin in treatment of experimental invasive infection by Candida parapsilosis: in vitro activity, (1->3)-beta-D-glucan and mannan serum levels, histopathological findings, and in vivo efficacy. Antimicrob Agents Chemother. 2011;55:4985-9.
63. Spreghini E, Orlando F, Tavanti A, et al. In vitro and in vivo effects of echinocandins against Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. J Antimicrob Chemother. 2012;67:2195-202.
64. Brzankalski GE, Najvar LK, Wiederhold NP, et al. Evaluation of aminocandin and caspofungin against Candida glabrata including isolates with reduced caspofungin susceptibility. J Antimicrob Chemother. 2008;62:1094-100.
65. Graybill JR, Bocanegra R, Luther M, et al. Treatment of murine Candida krusei or Candida glabrata infection with L-743,872. Antimicrob Agents Chemother. 1997;41:1937-9.
66. Graybill JR, Najvar LK, Luther MF, Fothergill AW. Treatment of murine disseminated candidiasis with L-743,872. Antimicrob Agents Chemother. 1997;41:1775-7.
67. Wiederhold NP, Najvar LK, Bocanegra R, et al. Comparison of anidulafungin's and fluconazole's in vivo activity in neutropenic and non-neutropenic models of invasive candidiasis. Clin Microbiol Infect. 2012;18:E20-3.
68. Warn PA, Sharp A, Parmar A, et al. Pharmacokinetics and pharmacodynamics of a novel triazole, isavuconazole: mathematical modeling, importance of tissue concentrations, and impact of immune status on antifungal effect. Antimicrob Agents Chemother. 2009;53:3453-61.
69. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020-9.
70. Andes D. Pharmacokinetics and pharmacodynamics of antifungals. Infect Dis Clin North Am. 2006;20:679-97.
71. Hope WW, Drusano GL. Antifungal pharmacokinetics and pharmacodynamics: bridging from the bench to bedside. Clin Microbiol Infect. 2009;15:602-12.
72. Betts RF, Nucci M, Talwar D, et al. A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis. 2009;48:1676-84.
73. Najvar LK, Bocanegra R, Wiederhold NP, et al. Therapeutic and prophylactic efficacy of aminocandin (IP960) against disseminated candidiasis in mice. Clin Microbiol Infect. 2008;14:595-600.
74. Wiederhold NP, Najvar LK, Bocanegra RA, et al. Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans. Antimicrob Agents Chemother. 2011;55:3254-60.
75. Ben-Ami R, Garcia-Effron G, Lewis RE, et al. Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J Infect Dis. 2011;204:626-35.
76. Ramage G, Saville SP, Thomas DP, Lopez-Ribot JL. Candida biofilms: an update. Eukaryot Cell. 2005;4:633-8.
77. Hawser SP, Baillie GS, Douglas LJ. Production of extracellular matrix by Candida albicans biofilms. J Med Microbiol. 1998;47:253-6.
78. Andes D, Nett J, Oschel P, et al. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun. 2004;72:6023-31.
79. Robbins N, Uppuluri P, Nett J, et al. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog. 2011;7:e1002257.
80. Uppuluri P, Nett J, Heitman J, Andes D. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob Agents Chemother. 2008;52:1127-32.
81. Nobile CJ, Fox EP, Nett JE, et al. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell. 2012;148:126-38.
82. Schinabeck MK, Long LA, Hossain MA, et al. Rabbit model of Candida albicans biofilm infection: liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother. 2004;48:1727-32.
83. Chandra J, Long L, Ghannoum MA, Mukherjee PK. A rabbit model for evaluation of catheter-associated fungal biofilms. Virulence. 2011;2:466-74.
84. Savage DC, Dubos RJ. Localization of indigenous yeast in the murine stomach. J Bacteriol. 1967;94:1811-6.
85. Kamai Y, Kubota M, Hosokawa T, et al. New model of oropharyngeal candidiasis in mice. Antimicrob Agents Chemother. 2001;45:3195-7.
86. Spellberg BJ, Ibrahim AS, Avanesian V, et al. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006;194:256-60.
87. Chiang LY, Sheppard DC, Bruno VM, et al. Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell Microbiol. 2007;9:233-45.
88. Zhu W, Phan QT, Boontheung P, et al. EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection. Proc Natl Acad Sci U S A. 2012;109:14194-9.
89. Nett JE, Marchillo K, Spiegel CA, Andes DR. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun. 2010;78:3650-9.
90. • Johnson CC, Yu A, Lee H, et al. Development of a contemporary animal model of Candida albicans-associated denture stomatitis using a novel intraoral denture system. Infect Immun. 2012;80:1736-43. New model of dental stomatitis in rats in which the development of the C. albicans biofilm on the removable prosthetic and tissue inflammation closely mimic that observed in humans.
91. Styrt B, Sugarman B. Estrogens and infection. Rev Infect Dis. 1991;13:1139-50.
92. Yano J, Noverr MC, Fidel Jr PL. Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins. Cytokine. 2012;58:118-28.
93. Yamaguchi N, Sonoyama K, Kikuchi H, et al. Gastric colonization of Candida albicans differs in mice fed commercial and purified diets. J Nutr. 2005;135:109-15.
94. Hardison SE, Herrera G, Young ML, et al. Protective immunity against pulmonary cryptococcosis is associated with STAT1-mediated classical macrophage activation. J Immunol. 2012;189:4060-8.
95. Hole CR, Wormley Jr FL. Vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: lessons learned from animal models. Front Microbiol. 2012;3:291.
96. Lortholary O, Improvisi L, Rayhane N, et al. Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection. Infect Immun. 1999;67:6314-20.
97. Lortholary O, Nicolas M, Soreda S, et al. Fluconazole, with or without dexamethasone for experimental cryptococcosis: impact of treatment timing. J Antimicrob Chemother. 1999;43:817-24.
98. Diamond DM, Bauer M, Daniel BE, et al. Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis. Antimicrob Agents Chemother. 1998;42:528-33.
99. Ding JC, Bauer M, Diamond DM, et al. Effect of severity of meningitis on fungicidal activity of flucytosine combined with fluconazole in a murine model of cryptococcal meningitis. Antimicrob Agents Chemother. 1997;41:1589-93.
100. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50:291-322.
101. Kirkpatrick WR, Najvar LK, Bocanegra R, et al. New guinea pig model of Cryptococcal meningitis. Antimicrob Agents Chemother. 2007;51:3011-3.
102. Carroll SF, Guillot L, Qureshi ST. Mammalian model hosts of cryptococcal infection. Comp Med. 2007;57:9-17.
103. Odom A, Del Poeta M, Perfect J, Heitman J. The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein. Antimicrob Agents Chemother. 1997;41:156-61.
104. Goldman D, Lee SC, Casadevall A. Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect Immun. 1994;62:4755-61.
105. Graybill JR, Ahrens J, Nealon T, Paque R. Pulmonary cryptococcosis in the rat. Am Rev Respir Dis. 1983;127:636-40.
106. Capilla J, Maffei CM, Clemons KV, et al. Experimental systemic infection with Cryptococcus neoformans var. grubii and Cryptococcus gattii in normal and immunodeficient mice. Med Mycol. 2006;44:601-10.
107. Sorrell TC. Cryptococcus neoformans variety gattii. Med Mycol. 2001;39:155-68.
108. Thompson 3rd GR, Wiederhold NP, Najvar LK, et al. A murine model of Cryptococcus gattii meningoencephalitis. J Antimicrob Chemother. 2012;67:1432-8.
109. Mitchell DH, Sorrell TC, Allworth AM, et al. Cryptococcal disease of the CNS in immunocompetent hosts: influence of cryptococcal variety on clinical manifestations and outcome. Clin Infect Dis. 1995;20:611-6.
110. Hospenthal DR, Bennett JE. Persistence of cryptococcomas on neuroimaging. Clin Infect Dis. 2000;31:1303-6.
111. • Chamilos G, Lionakis MS, Lewis RE, Kontoyiannis DP. Role of mini-host models in the study of medically important fungi. Lancet Infect Dis. 2007;7:42-55. Excellent review of invertebrate host models of invasive fungal infections.
112. Pukkila-Worley R, Holson E, Wagner F, Mylonakis E. Antifungal drug discovery through the study of invertebrate model hosts. Curr Med Chem. 2009;16:1588-95.
113. Lionakis MS, Lewis RE, May GS, et al. Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence. J Infect Dis. 2005;191:1188-95.
114. Cowen LE, Singh SD, Kohler JR, et al. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc Natl Acad Sci U S A. 2009;106:2818-23.
115. Tzou P, Ohresser S, Ferrandon D, et al. Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity. 2000;13:737-48.
116. Brennan CA, Anderson KV. Drosophila: the genetics of innate immune recognition and response. Annu Rev Immunol. 2004;22:457-83.
117. Ha EM, Oh CT, Bae YS, Lee WJ. A direct role for dual oxidase in Drosophila gut immunity. Science. 2005;310:847-50.
118. Chamilos G, Lionakis MS, Lewis RE, et al. Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species. J Infect Dis. 2006;193:1014-22.
119. Lamaris GA, Chamilos G, Lewis RE, Kontoyiannis DP. Virulence studies of Scedosporium and Fusarium species in Drosophila melanogaster. J Infect Dis. 2007;196:1860-4.
120. Lionakis MS. Drosophila and Galleria insect model hosts: new tools for the study of fungal virulence, pharmacology and immunology. Virulence. 2011;2:521-7.
121. Cronin SJ, Nehme NT, Limmer S, et al. Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection. Science. 2009;325:340-3.
122. Mylonakis E, Casadevall A, Ausubel FM. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi. PLoS Pathog. 2007;3:e101.
123. Mylonakis E, Moreno R, El Khoury JB, et al. Galleria mellonella as a model system to study Cryptococcus neoformans pathogenesis. Infect Immun. 2005;73:3842-50.
124. Vogel H, Altincicek B, Glockner G, Vilcinskas A. A comprehensive transcriptome and immune-gene repertoire of the lepidopteran model host Galleria mellonella. BMC Genomics. 2011;12:308.
125. London R, Orozco BS, Mylonakis E. The pursuit of cryptococcal pathogenesis: heterologous hosts and the study of cryptococcal host-pathogen interactions. FEMS Yeast Res. 2006;6:567-73.