Cellular and Molecular Life Sciences

, Volume 72, Issue 12, pp 2261–2287 | Cite as

Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies

  • Elizabeth J. Polvi
  • Xinliu Li
  • Teresa R. O’Meara
  • Michelle D. Leach
  • Leah E. CowenEmail author


Life-threatening invasive fungal infections are becoming increasingly common, at least in part due to the prevalence of medical interventions resulting in immunosuppression. Opportunistic fungal pathogens of humans exploit hosts that are immunocompromised, whether by immunosuppression or genetic predisposition, with infections originating from either commensal or environmental sources. Fungal pathogens are armed with an arsenal of traits that promote pathogenesis, including the ability to survive host physiological conditions and to switch between different morphological states. Despite the profound impact of fungal pathogens on human health worldwide, diagnostic strategies remain crude and treatment options are limited, with resistance to antifungal drugs on the rise. This review will focus on the global burden of fungal infections, the reservoirs of these pathogens, the traits of opportunistic yeast that lead to pathogenesis, host genetic susceptibilities, and the challenges that must be overcome to combat antifungal drug resistance and improve clinical outcome.


Opportunistic Fungi Yeast Pathogen Candida Cryptococcus Histoplasma Pneumocystis 



Allergic bronchopulmonary aspergillosis


Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy


Cyclic AMP


Centers for Disease Control and Prevention


Chronic granulomatous disease


C-type lectin receptors


Chronic mucocutaneous candidiasis


Central nervous system


Chronic obstructive pulmonary disease


C-reactive protein


Extracellular matrix


Gastrointestinally induced transition






Highly active antiretroviral therapies


Hyper-IgE syndrome


Heat shock protein






Immune reconstitution inflammatory syndrome




Mannose receptors


Nuclear factor-κB


Nitric oxide


Pathogen-associated molecular pattern


Pneumocystis pneumonia


Protein kinase A


Protein kinase C


Pattern recognition receptors


Secreted aspartyl proteinase


Transforming growth factor-β


Toll-like receptors


Tumor necrosis factor-α

Treg cell

Regulatory T cell


Vulvovaginal candidiasis



We thank the J. Andrew Alspaugh and Chad Rappleye labs for images and Cowen lab members for helpful discussions. EJP is supported by a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best CGS Doctoral Award, XL by a University of Toronto Fellowship, MDL by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), and LEC by a Ministry of Research and Innovation Early Researcher Award, Canada Research Chair in Microbial Genomics and Infectious Disease, Natural Sciences and Engineering Research Council Discovery Grant #355965, and by Canadian Institutes of Health Research Grants MOP-86452 and MOP-119520.


  1. 1.
    Wang DY, Kumar S, Hedges SB (1999) Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc Biol Sci 266:163–171PubMedCentralPubMedGoogle Scholar
  2. 2.
    Butterfield NJ (2005) Probable proterozoic fungi. Paleobiology 31:165–182Google Scholar
  3. 3.
    Hawksworth DL (2001) The magnitude of fungal diversity: the 1.5 million species estimate revisited. Mycol Res 105(12):1422–1432Google Scholar
  4. 4.
    DiGuistini S, Wang Y, Liao NY, Taylor G, Tanguay P, Feau N, Henrissat B, Chan SK, Hesse-Orce U, Alamouti SM, Tsui CK, Docking RT, Levasseur A, Haridas S, Robertson G, Birol I, Holt RA, Marra MA, Hamelin RC, Hirst M, Jones SJ, Bohlmann J, Breuil C (2011) Genome and transcriptome analyses of the mountain pine beetle-fungal symbiont Grosmannia clavigera, a lodgepole pine pathogen. Proc Natl Acad Sci USA 108:2504–2509PubMedCentralPubMedGoogle Scholar
  5. 5.
    Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ (2012) Emerging fungal threats to animal, plant and ecosystem health. Nature 484:186–194PubMedGoogle Scholar
  6. 6.
    Taylor LH, Latham SM, Woolhouse ME (2001) Risk factors for human disease emergence. Philos Trans R Soc Lond B Biol Sci 356:983–989PubMedCentralPubMedGoogle Scholar
  7. 7.
    Findley K, Oh J, Yang J, Conlan S, Deming C, Meyer JA, Schoenfeld D, Nomicos E, Park M, Program NIHISCCS, Kong HH, Segre JA (2013) Topographic diversity of fungal and bacterial communities in human skin. Nature 498:367–370PubMedCentralPubMedGoogle Scholar
  8. 8.
    Underhill DM, Iliev ID (2014) The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol 14:405–416PubMedCentralPubMedGoogle Scholar
  9. 9.
    Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, Gould C, Gemmen E, Dall T, American Academy of Dermatology A, Society for Investigative D (2006) The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol 55:490–500PubMedGoogle Scholar
  10. 10.
    Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC (2012) Hidden killers: human fungal infections. Sci Transl Med 4:165rv13PubMedGoogle Scholar
  11. 11.
    Pfaller MA, Diekema DJ (2010) Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 36:1–53PubMedGoogle Scholar
  12. 12.
    Brown GD, Denning DW, Levitz SM (2012) Tackling human fungal infections. Science 336:647PubMedGoogle Scholar
  13. 13.
    Bergman A, Casadevall A (2010) Mammalian endothermy optimally restricts fungi and metabolic costs. MBio 1(5):e00212-10PubMedCentralPubMedGoogle Scholar
  14. 14.
    Leach MD, Cowen LE (2013) Surviving the heat of the moment: a fungal pathogens perspective. PLoS Pathog 9:e1003163PubMedCentralPubMedGoogle Scholar
  15. 15.
    Garcia-Solache MA, Casadevall A (2010) Global warming will bring new fungal diseases for mammals. MBio 1(1):e00061-10PubMedCentralPubMedGoogle Scholar
  16. 16.
    McCusker JH, Clemons KV, Stevens DA, Davis RW (1994) Saccharomyces cerevisiae virulence phenotype as determined with CD-1 mice is associated with the ability to grow at 42 °C and form pseudohyphae. Infect Immun 62:5447–5455PubMedCentralPubMedGoogle Scholar
  17. 17.
    Bhabhra R, Miley MD, Mylonakis E, Boettner D, Fortwendel J, Panepinto JC, Postow M, Rhodes JC, Askew DS (2004) Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect Immun 72:4731–4740PubMedCentralPubMedGoogle Scholar
  18. 18.
    Lamoth F, Juvvadi PR, Fortwendel JR, Steinbach WJ (2012) Heat shock protein 90 is required for conidiation and cell wall integrity in Aspergillus fumigatus. Eukaryot Cell 11:1324–1332PubMedCentralPubMedGoogle Scholar
  19. 19.
    Odom A, Muir S, Lim E, Toffaletti DL, Perfect J, Heitman J (1997) Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J 16:2576–2589PubMedCentralPubMedGoogle Scholar
  20. 20.
    Havlickova B, Czaika VA, Friedrich M (2008) Epidemiological trends in skin mycoses worldwide. Mycoses 51:2–15PubMedGoogle Scholar
  21. 21.
    Sobel JD (2007) Vulvovaginal candidosis. Lancet 369:1961–1971PubMedGoogle Scholar
  22. 22.
    Marques SA, Robles AM, Tortorano AM, Tuculet MA, Negroni R, Mendes RP (2000) Mycoses associated with AIDS in the Third World. Med Mycol 38:269–279PubMedGoogle Scholar
  23. 23.
    Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23(4):525–530PubMedGoogle Scholar
  24. 24.
    Goldman DL, Khine H, Abadi J, Lindenberg DJ, Pirofski LA, Niang R, Casadevall A (2001) Serologic evidence for Cryptococcus neoformans infection in early childhood. Pediatrics 107(5):E66PubMedGoogle Scholar
  25. 25.
    Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, Centers for Disease Control and Prevention (CDC) (2008) McKenna MT (2008) Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and aids among children aged 18 months to <13 years—United States. MMWR Recomm Rep 57(10):1–12PubMedGoogle Scholar
  26. 26.
    Pyrgos V, Seitz AE, Steiner CA, Prevots DR, Williamson PR (2013) Epidemiology of Cryptococcal meningitis in the US: 1997–2009. PLoS ONE 8(2):e56269PubMedCentralPubMedGoogle Scholar
  27. 27.
    Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Stürmer T, Juliano JJ, Weber DJ, Perfect JR (2012) Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant. PLoS ONE 7(8):e43582PubMedCentralPubMedGoogle Scholar
  28. 28.
    Singh N, Dromer F, Perfect JR, Lortholary O (2008) Immunocompromised hosts: cryptococcosis in solid organ transplant recipients: current state of the science. Clin Infect Dis 47(10):1321–1327PubMedCentralPubMedGoogle Scholar
  29. 29.
    Bartlett KH, Cheng P-Y, Duncan C, Galanis E, Hoang L, Kidd S, Lee M-K, Lester S, MacDougall L, Mak S, Morshed M, Taylor M, Kronstad JW (2012) A decade of experience: Cryptococcus gattii in British Columbia. Mycopathologia 173(5–6):311–319PubMedGoogle Scholar
  30. 30.
    Byrnes EJ, Li W, Lewit Y, Ma H, Voelz K, Ren P, Carter DA, Chaturvedi V, Bildfell RJ, May RC, Heitman J (2010) Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 6(4):e1000850PubMedCentralPubMedGoogle Scholar
  31. 31.
    Galanis E, Macdougall L, Kidd S, Morshed M, British Colombia Cryptococcus gattii Working Group (2010) Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999–2007. Emerging Infect Dis 16(2):251–257PubMedCentralPubMedGoogle Scholar
  32. 32.
    Byrnes I, Edmond J, Bildfell RJ, Frank SA, Mitchell TG, Marr KA, Heitman J (2009) Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the pacific northwest in the United States. J Infect Dis 199(7):1081–1086PubMedCentralPubMedGoogle Scholar
  33. 33.
    Kunadharaju R, Choe U, Harris JR, Lockhart SR, Greene JN (2013) Cryptococcus gattii, Florida, USA, 2011. Emerg Infect 19(3):519–521Google Scholar
  34. 34.
    Perfect JR, Bicanic T (2014) Cryptococcosis diagnosis and treatment: what do we know now. Fungal Genet Biol. doi: 10.1016/j.fgb.2014.10.003 PubMedGoogle Scholar
  35. 35.
    Boulware DR, Bonham SC, Meya DB, Wiesner DL, Park GS, Kambugu A, Janoff EN, Bohjanen PR (2010) Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome. J Infect Dis 202(6):962–970PubMedCentralPubMedGoogle Scholar
  36. 36.
    Shelburne SA 3rd, Darcourt J, White AC Jr, Greenberg SB, Hamill RJ, Atmar RL, Visnegarwala F (2005) The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 40:1049–1052PubMedGoogle Scholar
  37. 37.
    Fetter A, Partisani M, Koenig H, Kremer M, Lang J-M (1993) Asymptomatic oral Candida albicans carriage in HIV-infection: frequency and predisposing factors. J Oral Pathol Med 22(2):57–59PubMedGoogle Scholar
  38. 38.
    Martins MD, Lozano-Chiu M, Rex JH (1998) Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Clin Infect Dis 27(5):1291–1294PubMedGoogle Scholar
  39. 39.
    Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ, Olyaei AJ, Marr KA, Pfaller MA, Chang C-H, Webster KM (2009) Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis 48(12):1695–1703PubMedGoogle Scholar
  40. 40.
    Koh AY, Kohler JR, Coggshall KT, Van Rooijen N, Pier GB (2008) Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog 4(2):e35PubMedCentralPubMedGoogle Scholar
  41. 41.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39(3):309–317PubMedGoogle Scholar
  42. 42.
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JAH, Wingard JR (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52(4):e56–e93PubMedGoogle Scholar
  43. 43.
    Nucci M, Anaissie E (2001) Revisiting the source of candidemia: skin or gut? Clin Infect Dis 33(12):1959–1967PubMedGoogle Scholar
  44. 44.
    Nett J, Andes DR (2006) Candida albicans biofilm development, modeling a host–pathogen interaction. Curr Opin Microbiol 9(4):340–345PubMedGoogle Scholar
  45. 45.
    Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot JL, Andes D, Cowen LE (2011) Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog 7:e1002257PubMedCentralPubMedGoogle Scholar
  46. 46.
    Hill JA, Ammar R, Torti D, Nislow C, Cowen LE (2013) Genetic and genomic architecture of the evolution of resistance to antifungal drug combinations. PLoS Genet 9(4):e1003390PubMedCentralPubMedGoogle Scholar
  47. 47.
    Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC (2010) Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog 6(9):e1001126PubMedCentralPubMedGoogle Scholar
  48. 48.
    Centres for Disease Control and Prevention (2013) Antibiotic resistance threats in the United States, 2013. U.S. Deparment of Health and Human Services. Centres for Disease Control and Prevention, AtlantaGoogle Scholar
  49. 49.
    Djawe K, Huang L, Daly KR, Levin L, Koch J, Schwartzman A, Fong S, Roth B, Subramanian A, Grieco K, Jarlsberg L, Walzer PD (2010) Serum antibody levels to the Pneumocystis jirovecii major surface glycoprotein in the diagnosis of P. jirovecii pneumonia in HIV+ patients. PLoS ONE 5(12):e14259PubMedCentralPubMedGoogle Scholar
  50. 50.
    Morris A, Norris KA (2012) Colonization by Pneumocystis jirovecii and its role in disease. Clin Microbiol Rev 25:297–317PubMedCentralPubMedGoogle Scholar
  51. 51.
    Pifer LL, Hughes WT, Stagno S, Woods D (1978) Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 61(1):35–41PubMedGoogle Scholar
  52. 52.
    Morris A, Lundgren JD, Masur H, Walzer PD, Hanson DL, Frederick T, Huang L, Beard CB, Kaplan JE (2004) Current epidemiology of Pneumocystis pneumonia. Emerging Infect Dis 10(10):1713–1720PubMedCentralPubMedGoogle Scholar
  53. 53.
    Masur H, Michelis MA, Greene JB, Onorato I, Stouwe RA, Holzman RS, Wormser G, Brettman L, Lange M, Murray HW, Cunningham-Rundles S (1981) An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med 305(24):1431–1438PubMedGoogle Scholar
  54. 54.
    Fisk DT, Meshnick S, Kazanjian PH (2003) Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis 36(1):70–78PubMedGoogle Scholar
  55. 55.
    Huang L, Cattamanchi A, Davis JL, Boon Sd, Kovacs J, Meshnick S, Miller RF, Walzer PD, Worodria W, Masur H, International HIV-associated Opportunistic Pneumonias (IHOP) Study; Lung HIV Study (2011) HIV-associated Pneumocystis pneumonia. Prom Am Thorac Soc 8(3):294–300Google Scholar
  56. 56.
    Kelley CF, Checkley W, Mannino DM, Franco-Paredes C, Del Rio C, Holguin F (2009) Trends in hospitalizations for AIDS-associated Pneumocystis jirovecii Pneumonia in the United States (1986 to 2005). Chest 136(1):190–197PubMedGoogle Scholar
  57. 57.
    Kyeyune R, den Boon S, Cattamanchi A, Davis JL, Worodria W, Yoo SD, Huang L (2010) Causes of early mortality in HIV-infected TB suspects in an East African referral hospital. J Acquir Immune Defic Syndr 55(4):446–450PubMedCentralPubMedGoogle Scholar
  58. 58.
    Sivam S, Sciurba FC, Lucht LA, Zhang Y, Duncan SR, Norris KA, Morris A (2011) Distribution of Pneumocystis jirovecii in lungs from colonized COPD patients. Diagn Microbiol Infect Dis 71(1):24–28PubMedCentralPubMedGoogle Scholar
  59. 59.
    Wald A, Leisenring W, van Burik JA, Bowden RA (1997) Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J Infect Dis 175:1459–1466PubMedGoogle Scholar
  60. 60.
    Marr KA, Carter RA, Crippa F, Wald A, Corey L (2002) Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34:909–917PubMedGoogle Scholar
  61. 61.
    Baddley JW, Andes DR, Marr KA, Kauffman CA, Kontoyiannis DP, Ito JI, Schuster MG, Brizendine KD, Patterson TF, Lyon GM, Boeckh M, Oster RA, Chiller T, Pappas PG (2013) Antifungal therapy and length of hospitalization in transplant patients with invasive aspergillosis. Med Mycol 51(2):128–135PubMedGoogle Scholar
  62. 62.
    Agarwal R, Chakrabarti A (2013) Allergic bronchopulmonary aspergillosis in asthma: epidemiological, clinical and therapeutic issues. Future Microbiol 8(11):1463–1474PubMedGoogle Scholar
  63. 63.
    Denning DW, Pleuvry A, Cole DC (2013) Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol 51(4):361–370PubMedGoogle Scholar
  64. 64.
    Kauffman CA (2007) Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 20(1):115–132PubMedCentralPubMedGoogle Scholar
  65. 65.
    Colombo AL, Tobón A, Restrepo A, Queiroz-Telles F, Nucci M (2011) Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol 49(8):785–798PubMedGoogle Scholar
  66. 66.
    Goodwin RAJ, Shapiro JL, Thurman GH, Thurman SS, des Prez RM (1980) Disseminated Histoplasmosis: clinical and pathologic correlations. Medicine (Baltimore) 59(1):1–33Google Scholar
  67. 67.
    Freitas DFS, Valle ACFD, da Silva MBT, Campos DP, Lyra MR, de Souza RV, Veloso VG, Zancopé-Oliveira RM, Bastos FI, Galhardo MCG (2014) Sporotrichosis: an emerging neglected opportunistic infection in HIV-infected patients in Rio de Janeiro, Brazil. PLoS Negl Trop Dis 8(8):e3110PubMedCentralPubMedGoogle Scholar
  68. 68.
    Sylvestre TF, Silva LRF, Cavalcante RDS, Moris DV, Venturini J, Vicentini AP, Carvalho LRD, Mendes RP (2014) Prevalence and serological diagnosis of relapse in Paracoccidioidomycosis patients. PLoS Negl Trop Dis 8(5):e2834PubMedCentralPubMedGoogle Scholar
  69. 69.
    Duong TA (1996) Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clin Infect Dis 23(1):125–130PubMedGoogle Scholar
  70. 70.
    Lee PPW, Chan K-W, Lee T-L, Ho MH-K, Chen X-Y, Li C-H, Chu K-M, Zeng H-S, Lau Y-L (2012) Penicilliosis in children without HIV infection–are they immunodeficient? Clin Infect Dis 54(2):e8–e19PubMedGoogle Scholar
  71. 71.
    Supparatpinyo K, Chiewchanvit S, Hirunsri P, Uthammachai C, Nelson KE, Sirisanthana T (1992) Penicillium marneffei infection in patients infected with human immunodeficiency virus. Clin Infect Dis 14(4):871–874PubMedGoogle Scholar
  72. 72.
    Vanittanakom N, Cooper CR, Fisher MC, Sirisanthana T (2006) Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev 19(1):95–110PubMedCentralPubMedGoogle Scholar
  73. 73.
    Bulterys PL, Le T, Quang VM, Nelson KE, Lloyd-Smith JO (2013) Environmental predictors and incubation period of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis 56(9):1273–1279PubMedCentralPubMedGoogle Scholar
  74. 74.
    Le T, Wolbers M, Chi NH, Quang VM, Chinh NT, Lan NPH, Lam PS, Kozal MJ, Shikuma CM, Day JN, Farrar J (2011) Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis 52(7):945–952PubMedCentralPubMedGoogle Scholar
  75. 75.
    Flaherman VJ, Hector R, Rutherford GW (2007) Estimating severe coccidioidomycosis in California. Emerg Infect Dis 13(7):1087–1090PubMedCentralPubMedGoogle Scholar
  76. 76.
    Brown J, Benedict K, Park B, Thompson G 3rd (2013) Coccidioidomycosis: epidemiology. Clin Epidemiol 5:185–197PubMedCentralPubMedGoogle Scholar
  77. 77.
    Santelli AC, Blair JE, Roust LR (2006) Coccidioidomycosis in patients with diabetes mellitus. Am J Med 119(11):964–969PubMedGoogle Scholar
  78. 78.
    Khuu D, Shafir S, Bristow B, Sorvillo F (2014) Blastomycosis mortality rates, United States, 1990–2010. Emerg Infect Dis 20(11):1789–1794PubMedCentralPubMedGoogle Scholar
  79. 79.
    Roy M, Benedict K, Deak E, Kirby MA, McNiel JT, Sickler CJ, Eckardt E, Marx RK, Heffernan RT, Meece JK, Klein BS, Archer JR, Theurer J, Davis JP, Park BJ (2013) A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering. Clin Infect Dis 57(5):655–662PubMedGoogle Scholar
  80. 80.
    Mendoza L, Vilela R, Voelz K, Ibrahim AS, Voigt K, Lee SC (2014) Human fungal pathogens of Mucorales and Entomophthorales. Cold Spring Harb Perspect Med. doi: 10.1101/cshperspect.a019562 PubMedGoogle Scholar
  81. 81.
    Chakrabarti A, Das A, Mandal J, Shivaprakash MR, George VK, Tarai B, Rao P, Panda N, Verma SC, Sakhuja V (2006) The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol 44(4):335–342PubMedGoogle Scholar
  82. 82.
    Lanternier F, Sun H-Y, Ribaud P, Singh N, Kontoyiannis DP, Lortholary O (2012) Mucormycosis in organ and stem cell transplant recipients. Clin Infect Dis 54(11):1629–1636PubMedGoogle Scholar
  83. 83.
    Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh TJ (2005) Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 41(5):634–653PubMedGoogle Scholar
  84. 84.
    Green JP, Karras DJ (2012) Update on emerging infections: news from the Centers for Disease Control and Prevention. Notes from the field: fatal fungal soft-tissue infections after a tornado–Joplin, Missouri, 2011. Ann Emerg Med 59(1):53–55PubMedGoogle Scholar
  85. 85.
    Bonifaz A, Vázquez-González D, Tirado-Sánchez A, Ponce-Olivera RM (2013) Cutaneous zygomycosis. Clin Dermatol 30(4):413–419Google Scholar
  86. 86.
    Barros MBDL, de Almeida Paes R, Schubach AO (2011) Sporothrix schenckii and Sporotrichosis. Clin Microbiol Rev 24(4):633–654PubMedCentralPubMedGoogle Scholar
  87. 87.
    Miceli MH, Diaz JA, Lee SA (2011) Emerging opportunistic yeast infections. Lancet Infect Dis 11:142–151PubMedGoogle Scholar
  88. 88.
    Girmenia C, Pagano L, Martino B, D’Antonio D, Fanci R, Specchia G, Melillo L, Buelli M, Pizzarelli G, Venditti M, Martino P, GIMEMA Infection Program (2005) Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin Microbiol 43(4):1818–1828PubMedCentralPubMedGoogle Scholar
  89. 89.
    Lin X, Heitman J (2006) The biology of the Cryptococcus neoformans species complex. Annu Rev Microbiol 60:69–105PubMedGoogle Scholar
  90. 90.
    Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC (2010) Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis 50:291–322PubMedGoogle Scholar
  91. 91.
    Idnurm A, Bahn YS, Nielsen K, Lin X, Fraser JA, Heitman J (2005) Deciphering the model pathogenic fungus Cryptococcus neoformans. Nat Rev Microbiol 3:753–764PubMedGoogle Scholar
  92. 92.
    Sorrell TC, Chen SC, Ruma P, Meyer W, Pfeiffer TJ, Ellis DH, Brownlee AG (1996) Concordance of clinical and environmental isolates of Cryptococcus neoformans var. gattii by random amplification of polymorphic DNA analysis and PCR fingerprinting. J Clin Microbiol 34:1253–1260PubMedCentralPubMedGoogle Scholar
  93. 93.
    Yamamoto Y, Kohno S, Koga H, Kakeya H, Tomono K, Kaku M, Yamazaki T, Arisawa M, Hara K (1995) Random amplified polymorphic DNA analysis of clinically and environmentally isolated Cryptococcus neoformans in Nagasaki. J Clin Microbiol 33:3328–3332PubMedCentralPubMedGoogle Scholar
  94. 94.
    Cogliati M (2013) Global molecular epidemiology of Cryptococcus neoformans and Cryptococcus gattii: an atlas of the molecular types. Scientifica (Cairo) 2013:675213Google Scholar
  95. 95.
    Litvintseva AP, Carbone I, Rossouw J, Thakur R, Govender NP, Mitchell TG (2011) Evidence that the human pathogenic fungus Cryptococcus neoformans var. grubii may have evolved in Africa. PLoS ONE 6:e19688PubMedCentralPubMedGoogle Scholar
  96. 96.
    Kidd SE, Chow Y, Mak S, Bach PJ, Chen H, Hingston AO, Kronstad JW, Bartlett KH (2007) Characterization of environmental sources of the human and animal pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States. Appl Environ Microbiol 73:1433–1443PubMedCentralPubMedGoogle Scholar
  97. 97.
    Chen SC, Meyer W, Sorrell TC (2014) Cryptococcus gattii infections. Clin Microbiol Rev 27:980–1024PubMedGoogle Scholar
  98. 98.
    Velagapudi R, Hsueh YP, Geunes-Boyer S, Wright JR, Heitman J (2009) Spores as infectious propagules of Cryptococcus neoformans. Infect Immun 77:4345–4355PubMedCentralPubMedGoogle Scholar
  99. 99.
    Coelho C, Bocca AL, Casadevall A (2014) The intracellular life of Cryptococcus neoformans. Annu Rev Pathol 9:219–238PubMedGoogle Scholar
  100. 100.
    Sabiiti W, May RC (2012) Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans. Future Microbiol 7:1297–1313PubMedGoogle Scholar
  101. 101.
    Garcia-Hermoso D, Janbon G, Dromer F (1999) Epidemiological evidence for dormant Cryptococcus neoformans infection. J Clin Microbiol 37:3204–3209PubMedCentralPubMedGoogle Scholar
  102. 102.
    Kronstad JW, Attarian R, Cadieux B, Choi J, D’Souza CA, Griffiths EJ, Geddes JM, Hu G, Jung WH, Kretschmer M, Saikia S, Wang J (2011) Expanding fungal pathogenesis: Cryptococcus breaks out of the opportunistic box. Nat Rev Microbiol 9:193–203PubMedGoogle Scholar
  103. 103.
    Nadrous HF, Antonios VS, Terrell CL, Ryu JH (2003) Pulmonary cryptococcosis in nonimmunocompromised patients. Chest 124:2143–2147PubMedGoogle Scholar
  104. 104.
    Voelz K, May RC (2010) Cryptococcal interactions with the host immune system. Eukaryot Cell 9:835–846PubMedCentralPubMedGoogle Scholar
  105. 105.
    Charlier C, Nielsen K, Daou S, Brigitte M, Chretien F, Dromer F (2009) Evidence of a role for monocytes in dissemination and brain invasion by Cryptococcus neoformans. Infect Immun 77:120–127PubMedCentralPubMedGoogle Scholar
  106. 106.
    Chen SH, Stins MF, Huang SH, Chen YH, Kwon-Chung KJ, Chang Y, Kim KS, Suzuki K, Jong AY (2003) Cryptococcus neoformans induces alterations in the cytoskeleton of human brain microvascular endothelial cells. J Med Microbiol 52:961–970PubMedGoogle Scholar
  107. 107.
    Chang YC, Stins MF, McCaffery MJ, Miller GF, Pare DR, Dam T, Paul-Satyaseela M, Kim KS, Kwon-Chung KJ (2004) Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier. Infect Immun 72:4985–4995PubMedCentralPubMedGoogle Scholar
  108. 108.
    Bicanic T, Harrison TS (2004) Cryptococcal meningitis. Br Med Bull 72:99–118PubMedGoogle Scholar
  109. 109.
    Chen SC, Slavin MA, Heath CH, Playford EG, Byth K, Marriott D, Kidd SE, Bak N, Currie B, Hajkowicz K, Korman TM, McBride WJ, Meyer W, Murray R, Sorrell TC, Australia, New Zealand Mycoses Interest Group-Cryptococcus S (2012) Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. Clin Infect Dis 55:789–798PubMedGoogle Scholar
  110. 110.
    Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of A (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535PubMedGoogle Scholar
  111. 111.
    Odds FC (1988) Candida and candidosis, 2nd edn. Baillière Tindall, LondonGoogle Scholar
  112. 112.
    Hube B (2004) From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans. Curr Opin Microbiol 7:336–341PubMedGoogle Scholar
  113. 113.
    Taylor BN, Harrer T, Pscheidl E, Schweizer A, Rollinghoff M, Schroppel K (2003) Surveillance of nosocomial transmission of Candida albicans in an intensive care unit by DNA fingerprinting. J Hosp Infect 55:283–289PubMedGoogle Scholar
  114. 114.
    Asmundsdottir LR, Erlendsdottir H, Haraldsson G, Guo H, Xu J, Gottfredsson M (2008) Molecular epidemiology of candidemia: evidence of clusters of smoldering nosocomial infections. Clin Infect Dis 47:e17–e24PubMedGoogle Scholar
  115. 115.
    Gow NA, Hube B (2012) Importance of the Candida albicans cell wall during commensalism and infection. Curr Opin Microbiol 15:406–412PubMedGoogle Scholar
  116. 116.
    Chen C, Pande K, French SD, Tuch BB, Noble SM (2011) An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis. Cell Host Microbe 10:118–135PubMedCentralPubMedGoogle Scholar
  117. 117.
    Pande K, Chen C, Noble SM (2013) Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet 45:1088–1091PubMedCentralPubMedGoogle Scholar
  118. 118.
    Perez JC, Kumamoto CA, Johnson AD (2013) Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit. PLoS Biol 11:e1001510PubMedCentralPubMedGoogle Scholar
  119. 119.
    Achkar JM, Fries BC (2010) Candida infections of the genitourinary tract. Clin Microbiol Rev 23:253–273PubMedCentralPubMedGoogle Scholar
  120. 120.
    de Leon EM, Jacober SJ, Sobel JD, Foxman B (2002) Prevalence and risk factors for vaginal Candida colonization in women with type 1 and type 2 diabetes. BMC Infect Dis 2:1PubMedCentralPubMedGoogle Scholar
  121. 121.
    Spinillo A, Capuzzo E, Acciano S, De Santolo A, Zara F (1999) Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. Am J Obstet Gynecol 180:14–17PubMedGoogle Scholar
  122. 122.
    Sobel JD, Faro S, Force RW, Foxman B, Ledger WJ, Nyirjesy PR, Reed BD, Summers PR (1998) Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 178:203–211PubMedGoogle Scholar
  123. 123.
    Edwards S (1996) Balanitis and balanoposthitis: a review. Genitourin Med 72:155–159PubMedCentralPubMedGoogle Scholar
  124. 124.
    Kauffman CA, Vazquez JA, Sobel JD, Gallis HA, McKinsey DS, Karchmer AW, Sugar AM, Sharkey PK, Wise GJ, Mangi R, Mosher A, Lee JY, Dismukes WE (2000) Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis 30:14–18PubMedGoogle Scholar
  125. 125.
    Bougnoux ME, Kac G, Aegerter P, D’Enfert C, Fagon JY, CandiRea Study G (2008) Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med 34:292–299PubMedGoogle Scholar
  126. 126.
    Lundstrom T, Sobel J (2001) Nosocomial candiduria: a review. Clin Infect Dis 32:1602–1607PubMedGoogle Scholar
  127. 127.
    Alvarez-Lerma F, Nolla-Salas J, Leon C, Palomar M, Jorda R, Carrasco N, Bobillo F, Group ES (2003) Candiduria in critically ill patients admitted to intensive care medical units. Intensive Care Med 29:1069–1076PubMedGoogle Scholar
  128. 128.
    Coronado-Castellote L, Jimenez-Soriano Y (2013) Clinical and microbiological diagnosis of oral candidiasis. J Clin Exp Dent 5:e279–e286PubMedCentralPubMedGoogle Scholar
  129. 129.
    Samaranayake LP, Keung Leung W, Jin L (2009) Oral mucosal fungal infections. Periodontol 49:39–59Google Scholar
  130. 130.
    Pankhurst CL (2013) Candidiasis (oropharyngeal). Clin Evid (Online) 2013:1304Google Scholar
  131. 131.
    de Repentigny L, Lewandowski D, Jolicoeur P (2004) Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev 17:729–759PubMedCentralPubMedGoogle Scholar
  132. 132.
    Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3:685–702PubMedGoogle Scholar
  133. 133.
    Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freifeld A, Anaissie EJ, Brumble LM, Herwaldt L, Ito J, Kontoyiannis DP, Lyon GM, Marr KA, Morrison VA, Park BJ, Patterson TF, Perl TM, Oster RA, Schuster MG, Walker R, Walsh TJ, Wannemuehler KA, Chiller TM (2010) Invasive fungal infections among organ transplant recipients: results of the transplant-associated infection surveillance network (TRANSNET). Clin Infect Dis 50:1101–1111PubMedGoogle Scholar
  134. 134.
    Eggimann P, Bille J, Marchetti O (2011) Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care 1:37PubMedCentralPubMedGoogle Scholar
  135. 135.
    Ellepola AN, Morrison CJ (2005) Laboratory diagnosis of invasive candidiasis. J Microbiol 43:65–84PubMedGoogle Scholar
  136. 136.
    Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640–3645PubMedCentralPubMedGoogle Scholar
  137. 137.
    Gigliotti F, Wright TW (2012) Pneumocystis: where does it live? PLoS Pathog 8:e1003025PubMedCentralPubMedGoogle Scholar
  138. 138.
    Durand-Joly I, El Aliouat M, Recourt C, Guyot K, Francois N, Wauquier M, Camus D, Dei-Cas E (2002) Pneumocystis carinii f. sp. hominis is not infectious for SCID mice. J Clin Microbiol 40:1862–1865PubMedCentralPubMedGoogle Scholar
  139. 139.
    Sinclair K, Wakefield AE, Banerji S, Hopkin JM (1991) Pneumocystis carinii organisms derived from rat and human hosts are genetically distinct. Mol Biochem Parasitol 45:183–184PubMedGoogle Scholar
  140. 140.
    Thomas CF Jr, Limper AH (2004) Pneumocystis pneumonia. N Engl J Med 350:2487–2498PubMedGoogle Scholar
  141. 141.
    Beard CB, Roux P, Nevez G, Hauser PM, Kovacs JA, Unnasch TR, Lundgren B (2004) Strain typing methods and molecular epidemiology of Pneumocystis pneumonia. Emerg Infect Dis 10:1729–1735PubMedCentralPubMedGoogle Scholar
  142. 142.
    Peterson JC, Cushion MT (2005) Pneumocystis: not just pneumonia. Curr Opin Microbiol 8:393–398PubMedGoogle Scholar
  143. 143.
    Wakefield AE, Lindley AR, Ambrose HE, Denis CM, Miller RF (2003) Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients. J Infect Dis 187:901–908PubMedGoogle Scholar
  144. 144.
    Larsen HH, von Linstow ML, Lundgren B, Hogh B, Westh H, Lundgren JD (2007) Primary Pneumocystis infection in infants hospitalized with acute respiratory tract infection. Emerg Infect Dis 13:66–72PubMedCentralPubMedGoogle Scholar
  145. 145.
    Morris A, Wei K, Afshar K, Huang L (2008) Epidemiology and clinical significance of pneumocystis colonization. J Infect Dis 197:10–17PubMedGoogle Scholar
  146. 146.
    Choukri F, Menotti J, Sarfati C, Lucet JC, Nevez G, Garin YJ, Derouin F, Totet A (2010) Quantification and spread of Pneumocystis jirovecii in the surrounding air of patients with Pneumocystis pneumonia. Clin Infect Dis 51:259–265PubMedGoogle Scholar
  147. 147.
    Wakefield AE (1996) DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J Clin Microbiol 34:1754–1759PubMedCentralPubMedGoogle Scholar
  148. 148.
    Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA, Infectious Diseases Society of America (2007) Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 45:807–825PubMedGoogle Scholar
  149. 149.
    Adenis A, Nacher M, Hanf M, Vantilcke V, Boukhari R, Blachet D, Demar M, Aznar C, Carme B, Couppie P (2014) HIV-associated histoplasmosis early mortality and incidence trends: from neglect to priority. PLoS Negl Trop Dis 8:e3100PubMedCentralPubMedGoogle Scholar
  150. 150.
    Adenis AA, Aznar C, Couppie P (2014) Histoplasmosis in HIV-infected patients: a review of new developments and remaining gaps. Curr Trop Med Rep 1:119–128PubMedCentralPubMedGoogle Scholar
  151. 151.
    Casadevall A, Pirofski LA (1999) Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity. Infect Immun 67:3703–3713PubMedCentralPubMedGoogle Scholar
  152. 152.
    Nicholls S, Leach MD, Priest CL, Brown AJ (2009) Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals. Mol Microbiol 74:844–861PubMedCentralPubMedGoogle Scholar
  153. 153.
    Leach MD, Tyc KM, Brown AJ, Klipp E (2012) Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans. PLoS ONE 7:e32467PubMedCentralPubMedGoogle Scholar
  154. 154.
    Nicholls S, MacCallum DM, Kaffarnik FA, Selway L, Peck SC, Brown AJ (2011) Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans. Fungal Genet Biol 48:297–305PubMedCentralPubMedGoogle Scholar
  155. 155.
    Leach MD, Cowen LE (2014) Membrane fluidity and temperature sensing are coupled via circuitry comprised of Ole1, Rsp5, and Hsf1 in Candida albicans. Eukaryot Cell 13:1077–1084PubMedCentralPubMedGoogle Scholar
  156. 156.
    O’Meara T, Cowen LE (2014) Hsp90-dependent regulatory circuitry controlling temperature-dependent fungal development and virulence. Cell Microbiol 16(4):473–481PubMedGoogle Scholar
  157. 157.
    Nichols CB, Perfect ZH, Alspaugh JA (2007) A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans. Mol Microbiol 63:1118–1130PubMedGoogle Scholar
  158. 158.
    Cheon SA, Jung KW, Chen YL, Heitman J, Bahn YS, Kang HA (2011) Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans. PLoS Pathog 7:e1002177PubMedCentralPubMedGoogle Scholar
  159. 159.
    O’Meara TR, Hay C, Price MS, Giles S, Alspaugh JA (2010) Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host. Eukaryot Cell 9:1193–1202PubMedCentralPubMedGoogle Scholar
  160. 160.
    Gerik KJ, Bhimireddy SR, Ryerse JS, Specht CA, Lodge JK (2008) PKC1 is essential for protection against both oxidative and nitrosative stresses, cell integrity, and normal manifestation of virulence factors in the pathogenic fungus Cryptococcus neoformans. Eukaryot Cell 7:1685–1698PubMedCentralPubMedGoogle Scholar
  161. 161.
    Hu G, Cheng PY, Sham A, Perfect JR, Kronstad JW (2008) Metabolic adaptation in Cryptococcus neoformans during early murine pulmonary infection. Mol Microbiol 69:1456–1475PubMedCentralPubMedGoogle Scholar
  162. 162.
    Leach M, Cowen L (2014) To sense or die: mechanisms of temperature sensing in fungal pathogens. Curr Fungal Infect Rep 8:185–191Google Scholar
  163. 163.
    Carratu L, Franceschelli S, Pardini CL, Kobayashi GS, Horvath I, Vigh L, Maresca B (1996) Membrane lipid perturbation modifies the set point of the temperature of heat shock response in yeast. Proc Natl Acad Sci USA 93:3870–3875PubMedCentralPubMedGoogle Scholar
  164. 164.
    Selvig K, Alspaugh JA (2011) pH response pathways in fungi: adapting to host-derived and environmental signals. Mycobiology 39:249–256PubMedCentralPubMedGoogle Scholar
  165. 165.
    Bensen ES, Martin SJ, Li M, Berman J, Davis DA (2004) Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. Mol Microbiol 54:1335–1351PubMedGoogle Scholar
  166. 166.
    Nobile CJ, Solis N, Myers CL, Fay AJ, Deneault JS, Nantel A, Mitchell AP, Filler SG (2008) Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell Microbiol 10:2180–2196PubMedCentralPubMedGoogle Scholar
  167. 167.
    De Bernardis F, Muhlschlegel FA, Cassone A, Fonzi WA (1998) The pH of the host niche controls gene expression in and virulence of Candida albicans. Infect Immun 66:3317–3325PubMedCentralPubMedGoogle Scholar
  168. 168.
    Davis D, Edwards JE Jr, Mitchell AP, Ibrahim AS (2000) Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun 68:5953–5959PubMedCentralPubMedGoogle Scholar
  169. 169.
    O’Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, Alspaugh JA (2010) Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog 6:e1000776PubMedCentralPubMedGoogle Scholar
  170. 170.
    Okagaki LH, Wang Y, Ballou ER, O’Meara TR, Bahn YS, Alspaugh JA, Xue C, Nielsen K (2011) Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli. Eukaryot Cell 10:1306–1316PubMedCentralPubMedGoogle Scholar
  171. 171.
    O’Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA (2013) Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. MBio 4(1):e00522-12PubMedCentralPubMedGoogle Scholar
  172. 172.
    O’Meara TR, Xu W, Selvig KM, O’Meara MJ, Mitchell AP, Alspaugh JA (2014) The Cryptococcus neoformans Rim101 transcription factor directly regulates genes required for adaptation to the host. Mol Cell Biol 34:673–684PubMedCentralPubMedGoogle Scholar
  173. 173.
    Feldmesser M, Kress Y, Novikoff P, Casadevall A (2000) Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection. Infect Immun 68:4225–4237PubMedCentralPubMedGoogle Scholar
  174. 174.
    Vylkova S, Carman AJ, Danhof HA, Collette JR, Zhou H, Lorenz MC (2011) The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH. MBio 2:e00055-11PubMedCentralPubMedGoogle Scholar
  175. 175.
    Derengowski Lda S, Paes HC, Albuquerque P, Tavares AH, Fernandes L, Silva-Pereira I, Casadevall A (2013) The transcriptional response of Cryptococcus neoformans to ingestion by Acanthamoeba castellanii and macrophages provides insights into the evolutionary adaptation to the mammalian host. Eukaryot Cell 12:761–774PubMedGoogle Scholar
  176. 176.
    Weinberg ED (2009) Iron availability and infection. Biochim Biophys Acta 1790:600–605PubMedGoogle Scholar
  177. 177.
    Tangen KL, Jung WH, Sham AP, Lian T, Kronstad JW (2007) The iron- and cAMP-regulated gene SIT1 influences ferrioxamine B utilization, melanization and cell wall structure in Cryptococcus neoformans. Microbiology 153:29–41PubMedGoogle Scholar
  178. 178.
    Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G, Ernst JF (2002) The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun 70:5246–5255PubMedCentralPubMedGoogle Scholar
  179. 179.
    Almeida RS, Wilson D, Hube B (2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9:1000–1012PubMedGoogle Scholar
  180. 180.
    Jung WH, Saikia S, Hu G, Wang J, Fung CK, D’Souza C, White R, Kronstad JW (2010) HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans. PLoS Pathog 6:e1001209PubMedCentralPubMedGoogle Scholar
  181. 181.
    Jung WH, Sham A, Lian T, Singh A, Kosman DJ, Kronstad JW (2008) Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog 4:e45PubMedCentralPubMedGoogle Scholar
  182. 182.
    Jung WH, Hu G, Kuo W, Kronstad JW (2009) Role of ferroxidases in iron uptake and virulence of Cryptococcus neoformans. Eukaryot Cell 8:1511–1520PubMedCentralPubMedGoogle Scholar
  183. 183.
    Jung WH, Sham A, White R, Kronstad JW (2006) Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans. PLoS Biol 4:e410PubMedCentralPubMedGoogle Scholar
  184. 184.
    Weissman Z, Shemer R, Conibear E, Kornitzer D (2008) An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans. Mol Microbiol 69:201–217PubMedGoogle Scholar
  185. 185.
    Santos R, Buisson N, Knight S, Dancis A, Camadro JM, Lesuisse E (2003) Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase. Microbiology 149:579–588PubMedGoogle Scholar
  186. 186.
    Navarathna DH, Roberts DD (2010) Candida albicans heme oxygenase and its product CO contribute to pathogenesis of candidemia and alter systemic chemokine and cytokine expression. Free Radic Biol Med 49:1561–1573PubMedCentralPubMedGoogle Scholar
  187. 187.
    Otterbein LE, Bach FH, Alam J, Soares M, Tao LuH, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422–428PubMedGoogle Scholar
  188. 188.
    Pendrak ML, Chao MP, Yan SS, Roberts DD (2004) Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin. J Biol Chem 279:3426–3433PubMedGoogle Scholar
  189. 189.
    Hwang LH, Mayfield JA, Rine J, Sil A (2008) Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization. PLoS Pathog 4:e1000044PubMedCentralPubMedGoogle Scholar
  190. 190.
    Hilty J, George Smulian A, Newman SL (2011) Histoplasma capsulatum utilizes siderophores for intracellular iron acquisition in macrophages. Med Mycol 49:633–642PubMedGoogle Scholar
  191. 191.
    Chao LY, Marletta MA, Rine J (2008) Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum. Biochemistry 47:7274–7283PubMedGoogle Scholar
  192. 192.
    Timmerman MM, Woods JP (2001) Potential role for extracellular glutathione-dependent ferric reductase in utilization of environmental and host ferric compounds by Histoplasma capsulatum. Infect Immun 69:7671–7678PubMedCentralPubMedGoogle Scholar
  193. 193.
    Nemecek JC, Wuthrich M, Klein BS (2006) Global control of dimorphism and virulence in fungi. Science 312:583–588PubMedGoogle Scholar
  194. 194.
    Nguyen VQ, Sil A (2008) Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator. Proc Natl Acad Sci USA 105:4880–4885PubMedCentralPubMedGoogle Scholar
  195. 195.
    Beyhan S, Gutierrez M, Voorhies M, Sil A (2013) A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen. PLoS Biol 11:e1001614PubMedCentralPubMedGoogle Scholar
  196. 196.
    Warenda AJ, Konopka JB (2002) Septin function in Candida albicans morphogenesis. Mol Biol Cell 13:2732–2746PubMedCentralPubMedGoogle Scholar
  197. 197.
    Sudbery P, Gow N, Berman J (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12:317–324PubMedGoogle Scholar
  198. 198.
    Xu XL, Lee RT, Fang HM, Wang YM, Li R, Zou H, Zhu Y, Wang Y (2008) Bacterial peptidoglycan triggers Candida albicans hyphal growth by directly activating the adenylyl cyclase Cyr1p. Cell Host Microbe 4:28–39PubMedGoogle Scholar
  199. 199.
    Brown V, Sexton JA, Johnston M (2006) A glucose sensor in Candida albicans. Eukaryot Cell 5:1726–1737PubMedCentralPubMedGoogle Scholar
  200. 200.
    Hudson DA, Sciascia QL, Sanders RJ, Norris GE, Edwards PJ, Sullivan PA, Farley PC (2004) Identification of the dialysable serum inducer of germ-tube formation in Candida albicans. Microbiology 150:3041–3049PubMedGoogle Scholar
  201. 201.
    Shapiro RS, Robbins N, Cowen LE (2011) Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75:213–267PubMedCentralPubMedGoogle Scholar
  202. 202.
    Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, Cowen LE (2009) Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol 19:621–629PubMedCentralPubMedGoogle Scholar
  203. 203.
    Bockmuhl DP, Ernst JF (2001) A potential phosphorylation site for an A-type kinase in the Efg1 regulator protein contributes to hyphal morphogenesis of Candida albicans. Genetics 157:1523–1530PubMedCentralPubMedGoogle Scholar
  204. 204.
    Cao F, Lane S, Raniga PP, Lu Y, Zhou Z, Ramon K, Chen J, Liu H (2006) The Flo8 transcription factor is essential for hyphal development and virulence in Candida albicans. Mol Biol Cell 17:295–307PubMedCentralPubMedGoogle Scholar
  205. 205.
    Lu Y, Su C, Liu H (2014) Candida albicans hyphal initiation and elongation. Trends Microbiol 22:707–714PubMedGoogle Scholar
  206. 206.
    Dalle F, Wachtler B, L’Ollivier C, Holland G, Bannert N, Wilson D, Labruere C, Bonnin A, Hube B (2010) Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes. Cell Microbiol 12:248–271PubMedGoogle Scholar
  207. 207.
    Rocha CR, Schroppel K, Harcus D, Marcil A, Dignard D, Taylor BN, Thomas DY, Whiteway M, Leberer E (2001) Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol Biol Cell 12:3631–3643PubMedCentralPubMedGoogle Scholar
  208. 208.
    Leberer E, Harcus D, Dignard D, Johnson L, Ushinsky S, Thomas DY, Schroppel K (2001) Ras links cellular morphogenesis to virulence by regulation of the MAP kinase and cAMP signalling pathways in the pathogenic fungus Candida albicans. Mol Microbiol 42:673–687PubMedGoogle Scholar
  209. 209.
    Park H, Myers CL, Sheppard DC, Phan QT, Sanchez AA, Edwards JE, Filler SG (2005) Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. Cell Microbiol 7:499–510PubMedGoogle Scholar
  210. 210.
    Murad AM, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D, Schnell N, Talibi D, Marechal D, Tekaia F, d’Enfert C, Gaillardin C, Odds FC, Brown AJ (2001) NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J 20:4742–4752PubMedCentralPubMedGoogle Scholar
  211. 211.
    Saville SP, Lazzell AL, Monteagudo C, Lopez-Ribot JL (2003) Engineered control of cell morphology in vivo reveals distinct roles for yeast and filamentous forms of Candida albicans during infection. Eukaryot Cell 2:1053–1060PubMedCentralPubMedGoogle Scholar
  212. 212.
    Hirakawa MP, Martinez DA, Sakthikumar S, Anderson MZ, Berlin A, Gujja S, Zeng Q, Zisson E, Wang JM, Greenberg JM, Berman J, Bennett RJ, Cuomo CA (2014) Genetic and phenotypic intra-species variation in Candida albicans. Genome Res. doi: 10.1101/gr.174623.114 PubMedGoogle Scholar
  213. 213.
    Vautier S, Drummond RA, Chen K, Murray GI, Kadosh D, Brown AJ, Gow NA, MacCallum DM, Kolls JK, Brown GD (2014) Candida albicans colonization and dissemination from the murine gastrointestinal tract: the influence of morphology and Th17 immunity. Cell Microbiol. doi: 10.1111/cmi.12388 PubMedCentralPubMedGoogle Scholar
  214. 214.
    Brand A (2012) Hyphal growth in human fungal pathogens and its role in virulence. Int J Microbiol. doi: 10.1155/2012/517529 PubMedCentralPubMedGoogle Scholar
  215. 215.
    Liu Y, Filler SG (2011) Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell 10:168–173PubMedCentralPubMedGoogle Scholar
  216. 216.
    Staab JF, Bradway SD, Fidel PL, Sundstrom P (1999) Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283:1535–1538PubMedGoogle Scholar
  217. 217.
    Hube B, Monod M, Schofield DA, Brown AJ, Gow NA (1994) Expression of seven members of the gene family encoding secretory aspartyl proteinases in Candida albicans. Mol Microbiol 14:87–99PubMedGoogle Scholar
  218. 218.
    White TC, Agabian N (1995) Candida albicans secreted aspartyl proteinases: isoenzyme pattern is determined by cell type, and levels are determined by environmental factors. J Bacteriol 177:5215–5221PubMedCentralPubMedGoogle Scholar
  219. 219.
    Cowen LE (2013) The fungal Achilles’ heel: targeting Hsp90 to cripple fungal pathogens. Curr Opin Microbiol 16(4):377–384PubMedGoogle Scholar
  220. 220.
    Prill SK, Klinkert B, Timpel C, Gale CA, Schroppel K, Ernst JF (2005) PMT family of Candida albicans: five protein mannosyltransferase isoforms affect growth, morphogenesis and antifungal resistance. Mol Microbiol 55:546–560PubMedGoogle Scholar
  221. 221.
    Sellam A, Askew C, Epp E, Tebbji F, Mullick A, Whiteway M, Nantel A (2010) Role of transcription factor CaNdt80p in cell separation, hyphal growth, and virulence in Candida albicans. Eukaryot Cell 9:634–644PubMedCentralPubMedGoogle Scholar
  222. 222.
    Huang G, Wang H, Chou S, Nie X, Chen J, Liu H (2006) Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci USA 103:12813–12818PubMedCentralPubMedGoogle Scholar
  223. 223.
    Miller MG, Johnson AD (2002) White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell 110:293–302PubMedGoogle Scholar
  224. 224.
    Forche A, Alby K, Schaefer D, Johnson AD, Berman J, Bennett RJ (2008) The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains. PLoS Biol 6:e110PubMedCentralPubMedGoogle Scholar
  225. 225.
    Kvaal C, Lachke SA, Srikantha T, Daniels K, McCoy J, Soll DR (1999) Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection. Infect Immun 67:6652–6662PubMedCentralPubMedGoogle Scholar
  226. 226.
    Si H, Hernday AD, Hirakawa MP, Johnson AD, Bennett RJ (2013) Candida albicans white and opaque cells undergo distinct programs of filamentous growth. PLoS Pathog 9:e1003210PubMedCentralPubMedGoogle Scholar
  227. 227.
    Sasse C, Hasenberg M, Weyler M, Gunzer M, Morschhauser J (2013) White-opaque switching of Candida albicans allows immune evasion in an environment-dependent fashion. Eukaryot Cell 12:50–58PubMedCentralPubMedGoogle Scholar
  228. 228.
    Kolotila MP, Diamond RD (1990) Effects of neutrophils and in vitro oxidants on survival and phenotypic switching of Candida albicans WO-1. Infect Immun 58:1174–1179PubMedCentralPubMedGoogle Scholar
  229. 229.
    Tao L, Du H, Guan G, Dai Y, Nobile CJ, Liang W, Cao C, Zhang Q, Zhong J, Huang G (2014) Discovery of a “white-gray-opaque” tristable phenotypic switching system in Candida albicans: roles of non-genetic diversity in host adaptation. PLoS Biol 12:e1001830PubMedCentralPubMedGoogle Scholar
  230. 230.
    Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ, Chretien F, Heitman J, Dromer F, Nielsen K (2010) Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathog 6:e1000953PubMedCentralPubMedGoogle Scholar
  231. 231.
    Zaragoza O, Garcia-Rodas R, Nosanchuk JD, Cuenca-Estrella M, Rodriguez-Tudela JL, Casadevall A (2010) Fungal cell gigantism during mammalian infection. PLoS Pathog 6:e1000945PubMedCentralPubMedGoogle Scholar
  232. 232.
    Zaragoza O, Nielsen K (2013) Titan cells in Cryptococcus neoformans: cells with a giant impact. Curr Opin Microbiol 16:409–413PubMedCentralPubMedGoogle Scholar
  233. 233.
    Okagaki LH, Nielsen K (2012) Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections. Eukaryot Cell 11:820–826PubMedCentralPubMedGoogle Scholar
  234. 234.
    Crabtree JN, Okagaki LH, Wiesner DL, Strain AK, Nielsen JN, Nielsen K (2012) Titan cell production enhances the virulence of Cryptococcus neoformans. Infect Immun 80:3776–3785PubMedCentralPubMedGoogle Scholar
  235. 235.
    Kojic EM, Darouiche RO (2004) Candida infections of medical devices. Clin Microbiol Rev 17:255–267PubMedCentralPubMedGoogle Scholar
  236. 236.
    Dongari-Bagtzoglou A, Kashleva H, Dwivedi P, Diaz P, Vasilakos J (2009) Characterization of mucosal Candida albicans biofilms. PLoS ONE 4:e7967PubMedCentralPubMedGoogle Scholar
  237. 237.
    Finkel JS, Mitchell AP (2011) Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118PubMedCentralPubMedGoogle Scholar
  238. 238.
    Douglas LJ (2003) Candida biofilms and their role in infection. Trends Microbiol 11:30–36PubMedGoogle Scholar
  239. 239.
    Zarnowski R, Westler WM, Lacmbouh GA, Marita JM, Bothe JR, Bernhardt J, Lounes-Hadj Sahraoui A, Fontaine J, Sanchez H, Hatfield RD, Ntambi JM, Nett JE, Mitchell AP, Andes DR (2014) Novel entries in a fungal biofilm matrix encyclopedia. MBio 5:e01333-14PubMedCentralPubMedGoogle Scholar
  240. 240.
    Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H, Cain MT, Hamaker J, Mitchell AP, Andes DR (2012) A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog 8(8):e1002848PubMedCentralPubMedGoogle Scholar
  241. 241.
    Nett J, Lincoln L, Marchillo K, Massey R, Holoyda K, Hoff B, VanHandel M, Andes D (2007) Putative role of β-1,3 glucans in Candida albicans biofilm resistance. Antimicrob Agents Chemother 51:510–520PubMedCentralPubMedGoogle Scholar
  242. 242.
    Taff HT, Mitchell KF, Edward JA, Andes DR (2013) Mechanisms of Candida biofilm drug resistance. Future Microbiol 8:1325–1337PubMedGoogle Scholar
  243. 243.
    Morrow B, Srikantha T, Soll DR (1992) Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans. Mol Cell Biol 12:2997–3005PubMedCentralPubMedGoogle Scholar
  244. 244.
    Naglik JR, Challacombe SJ, Hube B (2003) Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiol Mol Biol Rev 67:400–428PubMedCentralPubMedGoogle Scholar
  245. 245.
    de Repentigny L, Aumont F, Bernard K, Belhumeur P (2000) Characterization of binding of Candida albicans to small intestinal mucin and its role in adherence to mucosal epithelial cells. Infect Immun 68:3172–3179PubMedCentralPubMedGoogle Scholar
  246. 246.
    Schaller M, Borelli C, Korting HC, Hube B (2005) Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48:365–377PubMedGoogle Scholar
  247. 247.
    Leidich SD, Ibrahim AS, Fu Y, Koul A, Jessup C, Vitullo J, Fonzi W, Mirbod F, Nakashima S, Nozawa Y, Ghannoum MA (1998) Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem 273:26078–26086PubMedGoogle Scholar
  248. 248.
    Sebghati TS, Engle JT, Goldman WE (2000) Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence. Science 290:1368–1372PubMedGoogle Scholar
  249. 249.
    Beck MR, Dekoster GT, Cistola DP, Goldman WE (2009) NMR structure of a fungal virulence factor reveals structural homology with mammalian saposin B. Mol Microbiol 72:344–353PubMedGoogle Scholar
  250. 250.
    Bohse ML, Woods JP (2007) RNA interference-mediated silencing of the YPS3 gene of Histoplasma capsulatum reveals virulence defects. Infect Immun 75:2811–2817PubMedCentralPubMedGoogle Scholar
  251. 251.
    O’Meara TR, Alspaugh JA (2012) The Cryptococcus neoformans capsule: a sword and a shield. Clin Microbiol Rev 25:387–408PubMedCentralPubMedGoogle Scholar
  252. 252.
    Klutts JS, Doering TL (2008) Cryptococcal xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans plays a direct role in the synthesis of capsule polysaccharides. J Biol Chem 283:14327–14334PubMedCentralPubMedGoogle Scholar
  253. 253.
    Kozel TR, Levitz SM, Dromer F, Gates MA, Thorkildson P, Janbon G (2003) Antigenic and biological characteristics of mutant strains of Cryptococcus neoformans lacking capsular O acetylation or xylosyl side chains. Infect Immun 71:2868–2875PubMedCentralPubMedGoogle Scholar
  254. 254.
    Jong AY, Wu C-H, Chen H-M, Luo F, Kwon-Chung KJ, Chang YC, LaMunyon CW, Plaas A, Huang S-H (2007) Identification and characterization of CPS1 as a hyaluronic acid synthase contributing to the pathogenesis of Cryptococcus neoformans infection. Eukaryot Cell 6(8):1486–1496PubMedCentralPubMedGoogle Scholar
  255. 255.
    McFadden DC, Fries BC, Wang F, Casadevall A (2007) Capsule structural heterogeneity and antigenic variation in Cryptococcus neoformans. Eukaryot Cell 6:1464–1473PubMedCentralPubMedGoogle Scholar
  256. 256.
    Rivera J, Feldmesser M, Cammer M, Casadevall A (1998) Organ-dependent variation of capsule thickness in Cryptococcus neoformans during experimental murine infection. Infect Immun 66:5027–5030PubMedCentralPubMedGoogle Scholar
  257. 257.
    Palmer DA, Thompson JK, Li L, Prat A, Wang P (2006) Gib2, a novel Gβ-like/RACK1 homolog, functions as a Gβ subunit in cAMP signaling and is essential in Cryptococcus neoformans. J Biol Chem 281:32596–32605PubMedGoogle Scholar
  258. 258.
    Xue C, Hsueh YP, Chen L, Heitman J (2008) The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans. Mol Microbiol 70:379–395PubMedCentralPubMedGoogle Scholar
  259. 259.
    Xue C, Bahn YS, Cox GM, Heitman J (2006) G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol Biol Cell 17:667–679PubMedCentralPubMedGoogle Scholar
  260. 260.
    Vartivarian SE, Anaissie EJ, Cowart RE, Sprigg HA, Tingler MJ, Jacobson ES (1993) Regulation of cryptococcal capsular polysaccharide by iron. J Infect Dis 167:186–190PubMedGoogle Scholar
  261. 261.
    Klengel T, Liang W-J, Chaloupka J, Ruoff C, Schröppel K, Naglik JR, Eckert SE, Mogensen EG, Haynes K, Tuite MF, Levin LR, Buck J, Muhlschlegel FA (2005) Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence. Curr Biol 15:2021–2026PubMedCentralPubMedGoogle Scholar
  262. 262.
    Zaragoza O, Casadevall A (2004) Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online 6:10–15PubMedCentralPubMedGoogle Scholar
  263. 263.
    Vecchiarelli A, Pericolini E, Gabrielli E, Kenno S, Perito S, Cenci E, Monari C (2013) Elucidating the immunological function of the Cryptococcus neoformans capsule. Future Microbiol 8:1107–1116PubMedGoogle Scholar
  264. 264.
    Coelho C, Bocca AL, Casadevall A (2014) The tools for virulence of Cryptococcus neoformans. Adv Appl Microbiol 87:1–41PubMedGoogle Scholar
  265. 265.
    Rappleye CA, Engle JT, Goldman WE (2004) RNA interference in Histoplasma capsulatum demonstrates a role for α-(1,3)-glucan in virulence. Mol Microbiol 53:153–165PubMedGoogle Scholar
  266. 266.
    Rappleye CA, Eissenberg LG, Goldman WE (2007) Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor. Proc Natl Acad Sci USA 104:1366–1370PubMedCentralPubMedGoogle Scholar
  267. 267.
    Long KH, Gomez FJ, Morris RE, Newman SL (2003) Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J Immunol 170:487–494PubMedGoogle Scholar
  268. 268.
    Ehlers MR (2000) CR3: a general purpose adhesion-recognition receptor essential for innate immunity. Microbes Infect 2:289–294PubMedGoogle Scholar
  269. 269.
    Mihu MR, Nosanchuk JD (2012) Histoplasma virulence and host responses. Int J Microbiol. doi: 10.1155/2012/268123 PubMedCentralPubMedGoogle Scholar
  270. 270.
    Ma H, Croudace JE, Lammas DA, May RC (2006) Expulsion of live pathogenic yeast by macrophages. Curr Biol 16:2156–2160PubMedGoogle Scholar
  271. 271.
    Nicola AM, Robertson EJ, Albuquerque P, Derengowski Lda S, Casadevall A (2011) Nonlytic exocytosis of Cryptococcus neoformans from macrophages occurs in vivo and is influenced by phagosomal pH. MBio 2:e00167-11PubMedCentralPubMedGoogle Scholar
  272. 272.
    Alvarez M, Casadevall A (2006) Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages. Curr Biol 16:2161–2165PubMedGoogle Scholar
  273. 273.
    Bain JM, Lewis LE, Okai B, Quinn J, Gow NA, Erwig LP (2012) Non-lytic expulsion/exocytosis of Candida albicans from macrophages. Fungal Genet Biol 49:677–678PubMedCentralPubMedGoogle Scholar
  274. 274.
    Uwamahoro N, Verma-Gaur J, Shen HH, Qu Y, Lewis R, Lu J, Bambery K, Masters SL, Vince JE, Naderer T, Traven A (2014) The pathogen Candida albicans hijacks pyroptosis for escape from macrophages. MBio 5:e00003–e00014PubMedCentralPubMedGoogle Scholar
  275. 275.
    Wellington M, Koselny K, Sutterwala FS, Krysan DJ (2014) Candida albicans triggers NLRP3-mediated pyroptosis in macrophages. Eukaryot Cell 13:329–340PubMedCentralPubMedGoogle Scholar
  276. 276.
    Hromatka BS, Noble SM, Johnson AD (2005) Transcriptional response of Candida albicans to nitric oxide and the role of the YHB1 gene in nitrosative stress and virulence. Mol Biol Cell 16:4814–4826PubMedCentralPubMedGoogle Scholar
  277. 277.
    Ullmann BD, Myers H, Chiranand W, Lazzell AL, Zhao Q, Vega LA, Lopez-Ribot JL, Gardner PR, Gustin MC (2004) Inducible defense mechanism against nitric oxide in Candida albicans. Eukaryot Cell 3:715–723PubMedCentralPubMedGoogle Scholar
  278. 278.
    de Jesus-Berrios M, Liu L, Nussbaum JC, Cox GM, Stamler JS, Heitman J (2003) Enzymes that counteract nitrosative stress promote fungal virulence. Curr Biol 13:1963–1968PubMedGoogle Scholar
  279. 279.
    Missall TA, Pusateri ME, Donlin MJ, Chambers KT, Corbett JA, Lodge JK (2006) Posttranslational, translational, and transcriptional responses to nitric oxide stress in Cryptococcus neoformans: implications for virulence. Eukaryot Cell 5:518–529PubMedCentralPubMedGoogle Scholar
  280. 280.
    Nittler MP, Hocking-Murray D, Foo CK, Sil A (2005) Identification of Histoplasma capsulatum transcripts induced in response to reactive nitrogen species. Mol Biol Cell 16:4792–4813PubMedCentralPubMedGoogle Scholar
  281. 281.
    Nosanchuk JD, Valadon P, Feldmesser M, Casadevall A (1999) Melanization of Cryptococcus neoformans in murine infection. Mol Cell Biol 19:745–750PubMedCentralPubMedGoogle Scholar
  282. 282.
    Huffnagle GB, Chen GH, Curtis JL, McDonald RA, Strieter RM, Toews GB (1995) Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans. J Immunol 155:3507–3516PubMedGoogle Scholar
  283. 283.
    Casadevall A, Rosas AL, Nosanchuk JD (2000) Melanin and virulence in Cryptococcus neoformans. Curr Opin Microbiol 3:354–358PubMedGoogle Scholar
  284. 284.
    Rutherford JC (2014) The emerging role of urease as a general microbial virulence factor. PLoS Pathog 10:e1004062PubMedCentralPubMedGoogle Scholar
  285. 285.
    Olszewski MA, Noverr MC, Chen GH, Toews GB, Cox GM, Perfect JR, Huffnagle GB (2004) Urease expression by Cryptococcus neoformans promotes microvascular sequestration, thereby enhancing central nervous system invasion. Am J Pathol 164:1761–1771PubMedCentralPubMedGoogle Scholar
  286. 286.
    Cox GM, Mukherjee J, Cole GT, Casadevall A, Perfect JR (2000) Urease as a virulence factor in experimental cryptococcosis. Infect Immun 68:443–448PubMedCentralPubMedGoogle Scholar
  287. 287.
    Singh A, Panting RJ, Varma A, Saijo T, Waldron KJ, Jong A, Ngamskulrungroj P, Chang YC, Rutherford JC, Kwon-Chung KJ (2013) Factors required for activation of urease as a virulence determinant in Cryptococcus neoformans. MBio 4:e00220-13PubMedCentralPubMedGoogle Scholar
  288. 288.
    Osterholzer JJ, Surana R, Milam JE, Montano GT, Chen GH, Sonstein J, Curtis JL, Huffnagle GB, Toews GB, Olszewski MA (2009) Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response within the lung. Am J Pathol 174:932–943PubMedCentralPubMedGoogle Scholar
  289. 289.
    Navarathna DH, Das A, Morschhauser J, Nickerson KW, Roberts DD (2011) Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2. Microbiology 157:270–279PubMedCentralPubMedGoogle Scholar
  290. 290.
    Navarathna DH, Lionakis MS, Lizak MJ, Munasinghe J, Nickerson KW, Roberts DD (2012) Urea amidolyase (DUR1,2) contributes to virulence and kidney pathogenesis of Candida albicans. PLoS ONE 7:e48475PubMedCentralPubMedGoogle Scholar
  291. 291.
    Ghosh S, Navarathna DH, Roberts DD, Cooper JT, Atkin AL, Petro TM, Nickerson KW (2009) Arginine-induced germ tube formation in Candida albicans is essential for escape from murine macrophage line RAW 264.7. Infect Immun 77:1596–1605PubMedCentralPubMedGoogle Scholar
  292. 292.
    Romani L (2011) Immunity to fungal infections. Nat Rev Immunol 11:275–288PubMedGoogle Scholar
  293. 293.
    Netea MG, Brown GD, Kullberg BJ, Gow NA (2008) An integrated model of the recognition of Candida albicans by the innate immune system. Nat Rev Microbiol 6:67–78PubMedGoogle Scholar
  294. 294.
    Romani L (2004) Immunity to fungal infections. Nat Rev Immunol 4:1–23PubMedGoogle Scholar
  295. 295.
    Latge JP (2010) Tasting the fungal cell wall. Cell Microbiol 12:863–872PubMedGoogle Scholar
  296. 296.
    Lionakis MS, Netea MG (2013) Candida and host determinants of susceptibility to invasive candidiasis. PLoS Pathog 9:e1003079PubMedCentralPubMedGoogle Scholar
  297. 297.
    Gow N, Netea M, Munro CA, Ferwerda G, Bates S, Mora-Montes H, Walker LA, Jansen T, Jacobs L, Tsoni V, Brown G, Odds FC, Van der Meer JW, Brown A, Kullberg BJ (2007) Immune recognition of Candida albicans β-glucan by dectin 1. J Infect Dis 196(10):1565–1571PubMedCentralPubMedGoogle Scholar
  298. 298.
    Netea MG, Gow NA, Munro CA, Bates S, Collins C, Ferwerda G, Hobson RP, Bertram G, Hughes HB, Jansen T, Jacobs L, Buurman ET, Gijzen K, Williams DL, Torensma R, McKinnon A, MacCallum DM, Odds FC, Van der Meer JW, Brown AJ, Kullberg BJ (2006) Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and toll-like receptors. J Clin Invest 116:1642–1650PubMedCentralPubMedGoogle Scholar
  299. 299.
    Dan JM, Wang JP, Lee CK, Levitz SM (2008) Cooperative stimulation of dendritic cells by Cryptococcus neoformans mannoproteins and CpG oligodeoxynucleotides. PLoS ONE 3(4):e2046PubMedCentralPubMedGoogle Scholar
  300. 300.
    Brown GD (2011) Innate antifungal immunity: the key role of phagocytes. Annu Rev Immunol 29:1–21PubMedCentralPubMedGoogle Scholar
  301. 301.
    Bhatt VR, Viola GM, Ferrajoli A (2011) Invasive fungal infections in acute leukemia. Ther Adv Hematol 2:231–247PubMedCentralPubMedGoogle Scholar
  302. 302.
    Lionakis MS, Fischer BG, Lim JK, Swamydas M, Wan W, Richard Lee CC, Cohen JI, Scheinberg P, Gao JL, Murphy PM (2012) Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLoS Pathog 8:e1002865PubMedCentralPubMedGoogle Scholar
  303. 303.
    van de Veerdonk FL, Netea MG (2010) T-cell subsets and antifungal host defenses. Curr Fungal Infect Rep 4:238–243PubMedCentralPubMedGoogle Scholar
  304. 304.
    Armstrong-James D, Meintjes G, Brown GD (2014) A neglected epidemic: fungal infections in HIV/AIDS. Trends Microbiol 22:120–127PubMedGoogle Scholar
  305. 305.
    Pensieroso S, Galli L, Nozza S, Ruffin N, Castagna A, Tambussi G, Hejdeman B, Misciagna D, Riva A, Malnati M, Chiodi F, Scarlatti G (2013) B-cell subset alterations and correlated factors in HIV-1 infection. AIDS 27:1209–1217PubMedGoogle Scholar
  306. 306.
    Collini P, Noursadeghi M, Sabroe I, Miller RF, Dockrell DH (2010) Monocyte and macrophage dysfunction as a cause of HIV-1 induced dysfunction of innate immunity. Curr Mol Med 10:727–740PubMedGoogle Scholar
  307. 307.
    Olszewski MA, Huffnagle GB, McDonald RA, Lindell DM, Moore BB, Cook DN, Toews GB (2000) The role of macrophage inflammatory protein-1 α/CCL3 in regulation of T cell-mediated immunity to Cryptococcus neoformans infection. J Immunol 165:6429–6436PubMedGoogle Scholar
  308. 308.
    Wormley FL Jr, Perfect JR, Steele C, Cox GM (2007) Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infect Immun 75:1453–1462PubMedCentralPubMedGoogle Scholar
  309. 309.
    Hole CR, Wormley FL Jr (2012) Vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: lessons learned from animal models. Front Microbiol 3:291PubMedCentralPubMedGoogle Scholar
  310. 310.
    Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, Ho AW, Hai JH, Yu JJ, Jung JW, Filler SG, Masso-Welch P, Edgerton M, Gaffen SL (2009) Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 206:299–311PubMedCentralPubMedGoogle Scholar
  311. 311.
    Bixler SL, Mattapallil JJ (2013) Loss and dysregulation of Th17 cells during HIV infection. Clin Dev Immunol 2013:852418PubMedCentralPubMedGoogle Scholar
  312. 312.
    Rudner XL, Happel KI, Young EA, Shellito JE (2007) Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect Immun 75:3055–3061PubMedCentralPubMedGoogle Scholar
  313. 313.
    Netea MG, Sutmuller R, Hermann C, Van der Graaf CA, Van der Meer JW, van Krieken JH, Hartung T, Adema G, Kullberg BJ (2004) Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J Immunol 172:3712–3718PubMedGoogle Scholar
  314. 314.
    Kroetz DN, Deepe GS Jr (2010) CCR5 dictates the equilibrium of proinflammatory IL-17+ and regulatory Foxp3+ T cells in fungal infection. J Immunol 184:5224–5231PubMedCentralPubMedGoogle Scholar
  315. 315.
    Gildea LA, Gibbons R, Finkelman FD, Deepe GS Jr (2003) Overexpression of interleukin-4 in lungs of mice impairs elimination of Histoplasma capsulatum. Infect Immun 71:3787–3793PubMedCentralPubMedGoogle Scholar
  316. 316.
    Cenci E, Mencacci A, Del Sero G, Bacci A, Montagnoli C, d’Ostiani CF, Mosci P, Bachmann M, Bistoni F, Kopf M, Romani L (1999) Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J Infect Dis 180:1957–1968PubMedGoogle Scholar
  317. 317.
    Myers RC, Dunaway CW, Nelson MP, Trevor JL, Morris A, Steele C (2013) STAT4-dependent and -independent Th2 responses correlate with protective immunity against lung infection with Pneumocystis murina. J Immunol 190:6287–6294PubMedCentralPubMedGoogle Scholar
  318. 318.
    Bicanic T, Meintjes G, Rebe K, Williams A, Loyse A, Wood R, Hayes M, Jaffar S, Harrison TS (2009) Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr 51(2):130–134PubMedGoogle Scholar
  319. 319.
    Perfect JR (2012) The impact of the host on fungal infections. Am J Med 125:S39–S51PubMedGoogle Scholar
  320. 320.
    Boulware DR, Meya DB, Bergemann TL, Wiesner DL, Rhein J, Musubire A, Lee SJ, Kambugu A, Janoff EN, Bohjanen PR (2010) Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med 7:e1000384PubMedCentralPubMedGoogle Scholar
  321. 321.
    Lionakis MS (2012) Genetic susceptibility to fungal infections in humans. Curr Fungal Infect Rep 6:11–22PubMedCentralPubMedGoogle Scholar
  322. 322.
    Ferwerda B, Ferwerda G, Plantinga TS, Willment JA, van Spriel AB, Venselaar H, Elbers CC, Johnson MD, Cambi A, Huysamen C, Jacobs L, Jansen T, Verheijen K, Masthoff L, Morre SA, Vriend G, Williams DL, Perfect JR, Joosten LA, Wijmenga C, van der Meer JW, Adema GJ, Kullberg BJ, Brown GD, Netea MG (2009) Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 361:1760–1767PubMedCentralPubMedGoogle Scholar
  323. 323.
    Plantinga TS, van der Velden WJ, Ferwerda B, van Spriel AB, Adema G, Feuth T, Donnelly JP, Brown GD, Kullberg BJ, Blijlevens NM, Netea MG (2009) Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis 49:724–732PubMedGoogle Scholar
  324. 324.
    Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C, Salzer U, Pfeifer D, Veelken H, Warnatz K, Tahami F, Jamal S, Manguiat A, Rezaei N, Amirzargar AA, Plebani A, Hannesschlager N, Gross O, Ruland J, Grimbacher B (2009) A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 361:1727–1735PubMedCentralPubMedGoogle Scholar
  325. 325.
    Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, Toubiana J, Itan Y, Audry M, Nitschke P, Masson C, Toth B, Flatot J, Migaud M, Chrabieh M, Kochetkov T, Bolze A, Borghesi A, Toulon A, Hiller J, Eyerich S, Eyerich K, Gulacsy V, Chernyshova L, Chernyshov V, Bondarenko A, Grimaldo RM, Blancas-Galicia L, Beas IM, Roesler J, Magdorf K, Engelhard D, Thumerelle C, Burgel PR, Hoernes M, Drexel B, Seger R, Kusuma T, Jansson AF, Sawalle-Belohradsky J, Belohradsky B, Jouanguy E, Bustamante J, Bue M, Karin N, Wildbaum G, Bodemer C, Lortholary O, Fischer A, Blanche S, Al-Muhsen S, Reichenbach J, Kobayashi M, Rosales FE, Lozano CT, Kilic SS, Oleastro M, Etzioni A, Traidl-Hoffmann C, Renner ED, Abel L, Picard C, Marodi L, Boisson-Dupuis S, Puel A, Casanova JL (2011) Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 208:1635–1648PubMedCentralPubMedGoogle Scholar
  326. 326.
    van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, Arts P, Rosentul DC, Carmichael AJ, Smits-van der Graaf CA, Kullberg BJ, van der Meer JW, Lilic D, Veltman JA, Netea MG (2011) STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 365:54–61PubMedGoogle Scholar
  327. 327.
    Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332:65–68PubMedCentralPubMedGoogle Scholar
  328. 328.
    Kagami S, Rizzo HL, Kurtz SE, Miller LS, Blauvelt A (2010) IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 185:5453–5462PubMedCentralPubMedGoogle Scholar
  329. 329.
    Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, Kawamura N, Ariga T, Pasic S, Stojkovic O, Metin A, Karasuyama H (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448:1058–1062PubMedGoogle Scholar
  330. 330.
    Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O’Shea J, Holland SM, Paul WE, Douek DC (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773–776PubMedCentralPubMedGoogle Scholar
  331. 331.
    Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G, Chen A, Kim HS, Lloret MG, Schulze I, Ehl S, Thiel J, Pfeifer D, Veelken H, Niehues T, Siepermann K, Weinspach S, Reisli I, Keles S, Genel F, Kutukculer N, Camcioglu Y, Somer A, Karakoc-Aydiner E, Barlan I, Gennery A, Metin A, Degerliyurt A, Pietrogrande MC, Yeganeh M, Baz Z, Al-Tamemi S, Klein C, Puck JM, Holland SM, McCabe ER, Grimbacher B, Chatila TA (2009) Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol 124:1289–1302PubMedCentralPubMedGoogle Scholar
  332. 332.
    Mathis D, Benoist C (2009) Aire. Annu Rev Immunol 27:287–312PubMedGoogle Scholar
  333. 333.
    Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV, Ersvaer E, Perheentupa J, Erichsen MM, Bratanic N, Meloni A, Cetani F, Perniola R, Ergun-Longmire B, Maclaren N, Krohn KJ, Pura M, Schalke B, Strobel P, Leite MI, Battelino T, Husebye ES, Peterson P, Willcox N, Meager A (2010) Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med 207:299–308PubMedCentralPubMedGoogle Scholar
  334. 334.
    Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM (2000) Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 79:170–200Google Scholar
  335. 335.
    Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H (2000) Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 79:155–169Google Scholar
  336. 336.
    Aratani Y, Kura F, Watanabe H, Akagawa H, Takano Y, Suzuki K, Dinauer MC, Maeda N, Koyama H (2002) Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans. J Infect Dis 185:1833–1837PubMedGoogle Scholar
  337. 337.
    Cech P, Papathanassiou A, Boreux G, Roth P, Miescher PA (1979) Hereditary myeloperoxidase deficiency. Blood 53:403–411PubMedGoogle Scholar
  338. 338.
    Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, Olivier KN, Spalding C, Hughes S, Pittaluga S, Raffeld M, Sorbara LR, Elloumi HZ, Kuhns DB, Turner ML, Cowen EW, Fink D, Long-Priel D, Hsu AP, Ding L, Paulson ML, Whitney AR, Sampaio EP, Frucht DM, DeLeo FR, Holland SM (2010) Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115:1519–1529PubMedCentralPubMedGoogle Scholar
  339. 339.
    Arvanitis M, Anagnostou T, Fuchs BB, Caliendo AM, Mylonakis E (2014) Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev 27:490–526PubMedGoogle Scholar
  340. 340.
    Richardson MD, Warnock DW (2012) Fungal infection diagnosis and management, 4th edn. Wiley-Blackwell, Chichester, West Sussex, UKGoogle Scholar
  341. 341.
    Nguyen MH, Wissel MC, Shields RK, Salomoni MA, Hao B, Press EG, Shields RM, Cheng S, Mitsani D, Vadnerkar A, Silveira FP, Kleiboeker SB, Clancy CJ (2012) Performance of Candida real-time polymerase chain reaction, β-d-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis 54:1240–1248PubMedGoogle Scholar
  342. 342.
    Denning DW, Hope WW (2010) Therapy for fungal diseases: opportunities and priorities. Trends Microbiol 18:195–204PubMedGoogle Scholar
  343. 343.
    Gomez-Lopez A, Zaragoza O, Rodriguez-Tudela JL, Cuenca-Estrella M (2008) Pharmacotherapy of yeast infections. Expert Opin Pharmacother 9:2801–2816PubMedGoogle Scholar
  344. 344.
    Ghannoum MA, Rice LB (1999) Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 12:501–517PubMedCentralPubMedGoogle Scholar
  345. 345.
    Masia Canuto M, Gutierrez Rodero F (2002) Antifungal drug resistance to azoles and polyenes. Lancet Infect Dis 2:550–563PubMedGoogle Scholar
  346. 346.
    Deray G (2002) Amphotericin B nephrotoxicity. J Antimicrob Chemother 49(Suppl 1):37–41PubMedGoogle Scholar
  347. 347.
    Dupont B (2002) Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother 49(Suppl 1):31–36PubMedGoogle Scholar
  348. 348.
    Wong-Beringer A, Jacobs RA, Guglielmo BJ (1998) Lipid formulations of amphotericin B: clinical efficacy and toxicities. Clin Infect Dis 27:603–618PubMedGoogle Scholar
  349. 349.
    Vincent BM, Lancaster AK, Scherz-Shouval R, Whitesell L, Lindquist S (2013) Fitness trade-offs restrict the evolution of resistance to amphotericin B. PLoS Biol 11:e1001692PubMedCentralPubMedGoogle Scholar
  350. 350.
    Ellis D (2002) Amphotericin B: spectrum and resistance. J Antimicrob Chemother 49(Suppl 1):7–10PubMedGoogle Scholar
  351. 351.
    Sheehan DJ, Hitchcock CA, Sibley CM (1999) Current and emerging azole antifungal agents. Clin Microbiol Rev 12:40–79PubMedCentralPubMedGoogle Scholar
  352. 352.
    Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF, Infectious Diseases Society of America (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327–360PubMedGoogle Scholar
  353. 353.
    Pfaller MA (2012) Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125:S3–S13PubMedGoogle Scholar
  354. 354.
    Pound MW, Townsend ML, Drew RH (2010) Echinocandin pharmacodynamics: review and clinical implications. J Antimicrob Chemother 65:1108–1118PubMedGoogle Scholar
  355. 355.
    Denning DW (2003) Echinocandin antifungal drugs. Lancet 362:1142–1151PubMedGoogle Scholar
  356. 356.
    Holt SL, Drew RH (2011) Echinocandins: addressing outstanding questions surrounding treatment of invasive fungal infections. Am J Health Syst Pharm 68:1207–1220PubMedGoogle Scholar
  357. 357.
    Arendrup MC, Perlin DS (2014) Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis 27:484–492PubMedGoogle Scholar
  358. 358.
    Nanjappa SG, Klein BS (2014) Vaccine immunity against fungal infections. Curr Opin Immunol 28:27–33PubMedGoogle Scholar
  359. 359.
    Spellberg B (2011) Vaccines for invasive fungal infections. F1000 Med Rep 3:13PubMedCentralPubMedGoogle Scholar
  360. 360.
    NovaDigm Therapeutics, Inc (2013) Safety, tolerability, immunogenicity and efficacy of NDV-3A vaccine in preventing recurrent vulvovaginal candidiasis. Identifier: NCT01926028Google Scholar
  361. 361.
    Schmidt CS, White CJ, Ibrahim AS, Filler SG, Fu Y, Yeaman MR, Edwards JE Jr, Hennessey JP Jr (2012) NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. Vaccine 30:7594–7600PubMedCentralPubMedGoogle Scholar
  362. 362.
    De Bernardis F, Amacker M, Arancia S, Sandini S, Gremion C, Zurbriggen R, Moser C, Cassone A (2012) A virosomal vaccine against candidal vaginitis: immunogenicity, efficacy and safety profile in animal models. Vaccine 30:4490–4498PubMedGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Elizabeth J. Polvi
    • 1
  • Xinliu Li
    • 1
  • Teresa R. O’Meara
    • 1
  • Michelle D. Leach
    • 1
    • 2
  • Leah E. Cowen
    • 1
    Email author
  1. 1.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  2. 2.Aberdeen Fungal Group, Institute of Medical Sciences, School of Medical SciencesUniversity of AberdeenAberdeenUK

Personalised recommendations