Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches

Abstract

Seminal work by Louis Pasteur revealed the contribution of fungi—yeasts and microsporidia to agroindustry and disease in animals, respectively. More than 150 years later, the impact of fungi on human health and beyond is an ever-increasing issue, although often underestimated. Recent studies estimate that fungal infections, especially those caused by Candida, Cryptococcus and Aspergillus species, kill more than one million people annually. Indeed, these neglected infections are in general very difficult to cure and the associated mortality remains very high even when antifungal treatments exist. The development of new antifungals and diagnostic tools that are both necessary to fight fungal diseases efficiently, requires greater insights in the biology of the fungal pathogens of humans in the context of the infection, on their epidemiology, and on their role in the human mycobiota. We also need a better understanding of the host immune responses to fungal pathogens as well as the genetic basis for the increased sensitivity of some individuals to fungal infections. Here, we highlight some recent progress made in these different areas of research, in particular based on work conducted in our own laboratories. These progress should lay the ground for better management of fungal infections, as they provide opportunities for better diagnostic, vaccination, the development of classical antifungals but also strategies for targeting virulence factors or the host.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Hawksworth DL, Lücking R. Fungal Diversity Revisited: 2.2 to 3.8 Million Species. Microbiol Spectr. 2017;5:FUNK-0052-2016.

  2. 2.

    Nilsson RH, Anslan S, Bahram M, Wurzbacher C, Baldrian P, Tedersoo L. Mycobiome diversity: high-throughput sequencing and identification of fungi. Nat Rev Microbiol. 2019;17:95–109.

    CAS  PubMed  Google Scholar 

  3. 3.

    Cairns TC, Nai C, Meyer V. How a fungus shapes biotechnology: 100 years of Aspergillus niger research. Fungal Biol Biotechnol. 2018;5:13.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Spagnuolo M, Yaguchi A, Blenner M. Oleaginous yeast for biofuel and oleochemical production. Curr Opin Biotechnol. 2019;57:73–81.

    CAS  PubMed  Google Scholar 

  5. 5.

    Chang R. Bioactive polysaccharides from traditional Chinese medicine herbs as anticancer adjuvants. J Alter Complement Med. 2002;8:559–65.

    Google Scholar 

  6. 6.

    Rop O, Mlcek J, Jurikova T. Beta-glucans in higher fungi and their health effects. Nutr Rev. 2009;67:624–31.

    PubMed  Google Scholar 

  7. 7.

    Pelley RP, Strickland FM. Plants, polysaccharides, and the treatment and prevention of neoplasia. Crit Rev Oncog. 2000;11:189–225.

    CAS  PubMed  Google Scholar 

  8. 8.

    Nalley L, Tsiboe F, Durand-Morat A, Shew A, Thoma G. Economic and environmental impact of rice blast pathogen (Magnaporthe oryzae) alleviation in the United States. PLoS ONE. 2016;11:e0167295–e.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dita M, Barquero M, Heck D, Mizubuti ESG, Staver CP. Fusarium wilt of banana: current knowledge on epidemiology and research needs toward sustainable disease management. Front Plant Sci. 2018;9:1468.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Drees KP, Lorch JM, Puechmaille SJ, Parise KL, Wibbelt G, Hoyt JR, et al. Phylogenetics of a fungal invasion: origins and widespread dispersal of white-nose syndrome. mBio. 2017;8:e01941–17.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Grogan LF, Robert J, Berger L, Skerratt LF, Scheele BC, Castley JG, et al. Review of the amphibian immune response to chytridiomycosis, and future directions. Front Immunol. 2018;9:2536.

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bongomin F, Gago S, Oladele OR, Denning WD. Global and multi-national prevalence of fungal diseases—estimate precision. J Fungi. 2017;3:E57.

    Google Scholar 

  13. 13.

    Bongomin F, Gago S, Oladele RO, Denning DW. Global and multi-national prevalence of fungal diseases-estimate precision. J fungi. (Basel, Switz). 2017;3:57.

    Google Scholar 

  14. 14.

    Jackson BR, Beer KD, Chiller T, Benedict K. Estimation of direct healthcare costs of fungal diseases in the United States. 2018.

  15. 15.

    Kwon-Chung KJ, Fraser JA, Doering TL, Wang Z, Janbon G, Idnurm A, et al. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harb Perspect Med. 2014;4:a019760.

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Limper AH, Adenis A, Le T, Harrison TS. Fungal infections in HIV/AIDS. Lancet Infect Dis. 2017;17:e334–e43.

    PubMed  Google Scholar 

  17. 17.

    Sipsas NV, Kontoyiannis DP. Invasive fungal infections in patients with cancer in the Intensive Care Unit. Int J Antimicrob Agents. 2012;39:464–71.

    CAS  PubMed  Google Scholar 

  18. 18.

    Martinez R. New Trends in Paracoccidioidomycosis Epidemiology. J fungi (Basel, Switz). 2017;3:1.

    Google Scholar 

  19. 19.

    Adenis AA, Valdes A, Cropet C, McCotter OZ, Derado G, Couppie P, et al. Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis. 2018;18:1150–9.

    PubMed  Google Scholar 

  20. 20.

    Scorzoni L, de Paula E Silva AC, Marcos CM, Assato PA, de Melo WC, de Oliveira HC et al. Antifungal therapy: new advances in the understanding and treatment of mycosis. Front Microbiol. 2017;8:1–23.

    Google Scholar 

  21. 21.

    Fisher MC, Hawkins NJ, Sanglard D, Gurr SJ. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science. 2018;360:739.

    CAS  PubMed  Google Scholar 

  22. 22.

    Bastos RW, Carneiro HCS, Oliveira LVN, Rocha KM, Freitas GJC, Costa MC, et al. Environmental triazole induces cross-resistance to clinical drugs and affects morphophysiology and virulence of Cryptococcus gattii and C. neoformans. Antimicrob Agents Chemother. 2017;62:e01179–17.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Kneale M, Bartholomew JS, Denning DW, Davies E. Global access to antifungal therapy and its variable cost. J Antimicrob Chemother. 2016;71:3599–606.

    CAS  PubMed  Google Scholar 

  24. 24.

    Casadevall A. Determinants of virulence in the pathogenic fungi. Fungal Biol Rev. 2007;21:130–2.

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Jones T, Federspiel NA, Chibana H, Dungan J, Kalman S, Magee BB, et al. The diploid genome sequence of Candida albicans. Proc Natl Acad Sci USA. 2004;101:7329–34.

    CAS  PubMed  Google Scholar 

  26. 26.

    Dujon B, Sherman D, Fisher G, Durrens P, Casaregola S, Lafontaine I, et al. Genome evolution in yeasts. Nature. 2004;430:35–44.

    PubMed  Google Scholar 

  27. 27.

    Janbon G, Ormerod KL, Paulet D, Byrnes EJ III, Chatterjee G, Yadav V, et al. Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genet. 2014;10:e1004261.

    PubMed  PubMed Central  Google Scholar 

  28. 28.

    Nierman W, Pain A, Anderson M, Wortman J, Kim H, Arroyo J, et al. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005;438:1151–6.

    CAS  PubMed  Google Scholar 

  29. 29.

    Liu OW, Chun CD, Chow ED, Chen C, Madhani HD, Noble SM. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell. 2008;135:174–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, et al. Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol. 2003;50:167–81.

    CAS  PubMed  Google Scholar 

  31. 31.

    Schwarzmüller T, Ma B, Hiller E, Istel F, Tscherner M, Brunke S, et al. Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. PLoS Pathog. 2014;10:e1004211.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Rayner S, Bruhn S, Vallhov H, Andersson A, Billmyre RB, Scheynius A. Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis. Sci Rep. 2017;7:39742.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Jöchl C, Rederstorff M, Hertel J, Stadler PF, Hofacker IL, Schrettl M, et al. Small ncRNA transcriptome analysis from Aspergillus fumigatus suggests a novel mechanism for regulation of protein synthesis. Nucleic Acids Res. 2008;36:2677–89.

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Sellam A, Hogues H, Askew C, Tebbji F, van het Hoog M, Lavoie H, et al. Experimental annotation of the human pathogen Candida albicans coding and noncoding transcribed regions using high-resolution tiling arrays. Genome Biol. 2010;11:R71.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Yuan J, Wang Z, Xing J, Yang Q, Chen X-L. Genome-wide Identification and characterization of circular RNAs in the rice blast fungus Magnaporthe oryzae. Sci Rep. 2018;8:6757.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Chacko N, Zhao Y, Yang E, Wang L, Cai JJ, Lin X. The lncRNA RZE1 controls cryptococcal morphological transition. PLoS Genet. 2015;11:e1005692.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Chang Z, Billmyre RB, Lee SC, Heitman J. Broad antifungal resistance mediated by RNAi-dependent epimutation in the basal human fungal pathogen Mucor circinelloides. PLoS Genet. 2019;15:e1007957–e.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Calo S, Shertz-Wall C, Lee SC, Bastidas RJ, Nicolás FE, Granek JA, et al. Antifungal drug resistance evoked via RNAi-dependent epimutations. Nature. 2014;513:555–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Wang X, Hsueh YP, Li W, Floyd A, Skalsky R, Heitman J. Sex-induced silencing defends the genome of Cryptococcus neoformans via RNAi. Genes Dev. 2010;24:2566–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Janbon G, Maeng S, Yang DH, Ko YJ, Jung KW, Moyrand F, et al. Characterizing the role of RNA silencing components in Cryptococcus neoformans. Fungal Genet Biol. 2010;47:1070–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Gonzalez-Hilarion S, Paulet D, Lee K-T, Hon C-C, Lechat P, Mogensen E, et al. Intron retention-dependent gene regulation in Cryptococcus neoformans. Sci Rep. 2016;6:32252.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Stajich JE, Dietrich FS, Roy SW. Comparative genomic analysis of fungal genomes reveals intron-rich ancestors. Genome Biol. 2007;8:R223.

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Pelechano V, Wei W, Steinmetz LM. Extensive transcriptional heterogeneity revealed by isoform profiling. Nature. 2013;497:127–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Thodberg M, Thieffry A, Bornholdt J, Boyd M, Holmberg C, Azad A. et al. Comprehensive profiling of the fission yeast transcription start site activity during stress and media response. Nucleic Acids Res. 2019;47:1671–91.

    PubMed  Google Scholar 

  45. 45.

    Yue Y, Liu J, He C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015;29:1343–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Liu H, Li Y, Chen D, Qi Z, Wang Q, Wang J, et al. A-to-I RNA editing is developmentally regulated and generally adaptive for sexual reproduction in Neurospora crassa. Proc Natl Acad Sci USA. 2017;114:E7756–E65.

    CAS  PubMed  Google Scholar 

  47. 47.

    Kaur JN, Panepinto JC. Morphotype-specific effector functions of Cryptococcus neoformans PUM1. Sci Rep. 2016;6:23638.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Verma S, Idnurm A. The Uve1 endonuclease Is regulated by the white collar complex to protect Cryptococcus neoformans from UV Damage. PLoS Genet. 2013;9:e1003769.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Fan G, Sun Q, Li W, Shi W, Li X, Wu L et al. The global catalogue of microorganisms 10K type strain sequencing project: closing the genomic gaps for the validly published prokaryotic and fungi species. Gigascience. 2018;7:1–4.

    PubMed  Google Scholar 

  50. 50.

    Garcia-Hermoso D, Criscuolo A, Lee SC, Legrand M, Chaouat M, Denis B, et al. Outbreak of invasive wound mucormycosis in a burn unit due to multiple strains of mucor circinelloides f. circinelloides resolved by whole-genome sequencing. mBio. 2018;9:e00573–18.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Vaux S, Criscuolo A, Desnos-Ollivier M, Diancourt L, Tarnaud C, Vandenbogaert M, et al. Multicenter Outbreak of Infections by Saprochaete clavata an Unrecognized Opportunistic Fungal Pathogen. mBio. 2014;5:e02309–14.

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Desjardins CA, Giamberardino C, Sykes SM, Yu C-H, Tenor JL, Chen Y, et al. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res. 2017;27:1207–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Rhodes J, Desjardins CA, Sykes SM, Beale MA, Vanhove M, Sakthikumar S, et al. Tracing genetic exchange and biogeography of Cryptococcus neoformans var. grubii at the global population level. Genetics. 2017;207:327–46. https://doi.org/10.1534/genetics.117.203836.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Ropars J, Maufrais C, Diogo D, Marcet-Houben M, Perin A, Sertour N, et al. Gene flow contributes to diversification of the major fungal pathogen Candida albicans. Nat Commun. 2018;9:2253.

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Odds FC, Bougnoux M-E, Shaw DJ, Bain JM, Davidson AD, Diogo D, et al. Molecular phylogenetics of Candida albicans. Eukaryot Cell. 2007;6:1041–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Odds FC. Molecular phylogenetics and epidemiology of Candida albicans. Future Microbiol. 2009;5:67–79.

    Google Scholar 

  57. 57.

    Ene IV, Bennett RJ. The cryptic sexual strategies of human fungal pathogens. Nat Rev Microbiol. 2014;12:239.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Hirakawa MP, Martinez DA, Sakthikumar S, Anderson MZ, Berlin A, Gujja S, et al. Genetic and phenotypic intra-species variation in Candida albicans. Genome Res. 2015;25:413–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Bougnoux ME, Diogo D, François N, Sendid B, Veirmeire S, Colombel JF, et al. Multilocus sequence typing reveals intrafamilial transmission and microevolutions of Candida albicans isolates from the human digestive tract. J Clin Microbiol. 2006;44:1810–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, et al. Complementary adhesin function in C. albicans biofilm formation. Curr Biol: Cb. 2008;18:1017–24.

    CAS  PubMed  Google Scholar 

  61. 61.

    Coste A, Selmecki A, Forche A, Diogo D, Bougnoux M-E, d’Enfert C, et al. Genotypic evolution of azole resistance mechanisms in sequential Candida albicans isolates. Eukaryot Cell. 2007;6:1889–904.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Selmecki A, Forche A, Berman J. Aneuploidy and isochromosome formation in drug-resistant Candida albicans. Sci (New Y, NY). 2006;313:367–70.

    CAS  Google Scholar 

  63. 63.

    Stone NRH, Rhodes J, Fisher MC, Mfinanga S, Kivuyo S, Rugemalila J, et al. Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis. J Clin Invest. 2019;129:999–1014.

    PubMed  PubMed Central  Google Scholar 

  64. 64.

    Morrow CA, Fraser JA. Ploidy variation as an adaptive mechanism in human pathogenic fungi. Semin Cell Dev Biol. 2013;24:339–46.

    CAS  PubMed  Google Scholar 

  65. 65.

    Bennett RJ, Forche A, Berman J. Rapid mechanisms for generating genome diversity: whole ploidy shifts, aneuploidy, and loss of heterozygosity. Cold Spring Harb Perspect Med. 2014;4:a019604.

    PubMed  PubMed Central  Google Scholar 

  66. 66.

    Kim SH, Clark ST, Surendra A, Copeland JK, Wang PW, Ammar R, et al. Global analysis of the fungal microbiome in cystic fibrosis patients reveals loss of function of the transcriptional repressor nrg1 as a mechanism of pathogen adaptation. PLoS Pathog. 2015;11:e1005308–e.

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Tso GHW, Reales-Calderon JA, Tan ASM, Sem X, Le GTT, Tan TG, et al. Experimental evolution of a fungal pathogen into a gut symbiont. Science. 2018;362:589.

    CAS  PubMed  Google Scholar 

  68. 68.

    Chauvel M, Nesseir A, Cabral V, Znaidi S, Goyard S, Bachellier-Bassi S, et al. A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness. PLoS One. 2012;7:e45912–e.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Gow NAR, van de Veerdonk FL, Brown AJP, Netea MG. Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol. 2011;10:112–22.

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Böttcher B, Pöllath C, Staib P, Hube B, Brunke S. Candida species rewired hyphae developmental programs for chlamydospore formation. Front Microbiol. 2016;7:1697.

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Shapiro RS, Robbins N, Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev: Mmbr. 2011;75:213–67.

    CAS  PubMed  Google Scholar 

  72. 72.

    Sudbery PE. Growth of Candida albicans hyphae. Nat Rev Microbiol. 2011;9:737.

    CAS  PubMed  Google Scholar 

  73. 73.

    Hoyer LL, Cota E. Candida albicans agglutinin-like sequence (Als) family vignettes: a review of Als protein structure and function. Front Microbiol. 2016;7:280.

    PubMed  PubMed Central  Google Scholar 

  74. 74.

    Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR, Welch WH, et al. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol. 2007;5:e64–e.

    PubMed  PubMed Central  Google Scholar 

  75. 75.

    Moreno-Ruiz E, Galán-Díez M, Zhu W, Fernández-Ruiz E, d’Enfert C, Filler SG, et al. Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol. 2009;11:1179–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Myers C, Phan QT, Avanesian V, Ibrahim AS, Edwards JE Jr., Yeaman MR, 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.

    PubMed  Google Scholar 

  77. 77.

    Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, et al. Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature. 2016;532:64–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Zheng X, Wang Y, Wang Y. Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis. EMBO J. 2004;23:1845–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Bishop A, Lane R, Beniston R, Chapa-y-Lazo B, Smythe C, Sudbery P. Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinase. EMBO J. 2010;29:2930–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Noble SM, French S, Kohn L, Chen V, Johnson AD. Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet. 2010;42:590–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Znaidi S, Nesseir A, Chauvel M, Rossignol T, d’Enfert C. A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence. PLoS Pathog. 2013;9:e1003519–e.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Basso V, Znaidi S, Lagage V, Cabral V, Schoenherr F, LeibundGut-Landmann S, et al. The two-component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis-induced ROS accumulation. Mol Microbiol. 2017;106:157–82.

    CAS  PubMed  Google Scholar 

  83. 83.

    Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday AD, et al. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell . 2012;148:126–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Fox EP, Bui CK, Nett JE, Hartooni N, Mui MC, Andes DR, et al. An expanded regulatory network temporally controls Candida albicans biofilm formation. Mol Microbiol. 2015;96:1226–39.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Bose I, Reese AJ, Ory JJ, Janbon G, Doering TL. A yeast under cover: the capsule of Cryptococcus neoformans. Eukaryot Cell. 2003;2:655–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Doering TL. How Sweet it is! Cell Wall Biogenesis and Polysaccharide Capsule Formation in Cryptococcus neoformans. Ann Rev Microbiol. 2009;63:223–47.

    CAS  Google Scholar 

  87. 87.

    Moyrand F, Fontaine T, Janbon G. Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence. Mol Microbiol. 2007;64:771–81.

    CAS  PubMed  Google Scholar 

  88. 88.

    O’Meara TR, Alspaugh JA. The Cryptococcus neoformans capsule: a sword and a shield. Clin Microbiol Rev. 2012;25:387–408.

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Chun CD, Brown JCS, Madhani HD. A major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by Cryptococcus neoformans. Cell Host Microbe. 2011;9:243–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Zaragoza O, Nielsen K. Titan cells in Cryptococcus neoformans: Cells with a giant impact. Curr Opin Microbiol. 2013;16:409–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Hommel B, Mukaremera L, Cordero RJB, Coelho C, Desjardins CA, Sturny-Leclère A, et al. Titan cells formation in Cryptococcus neoformans is finely tuned by environmental conditions and modulated by positive and negative genetic regulators. PLoS Pathog. 2018;14:e1006982.

    PubMed  PubMed Central  Google Scholar 

  92. 92.

    Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I, Zaballos Á, et al. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog. 2018;14:e1007007.

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Dambuza IM, Drake T, Chapuis A, Zhou X, Correia J, Taylor-Smith L, et al. The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis. PLoS Pathog. 2018;14:e1006978–e.

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Ghez D, Calleja A, Protin C, Baron M, Ledoux M-P, Damaj G, et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood. 2018;131:1955.

    CAS  PubMed  Google Scholar 

  95. 95.

    Pilmis B, Puel A, Lortholary O, Lanternier F. New clinical phenotypes of fungal infections in special hosts. Clin Microbiol Infect. 2016;22:681–7.

    CAS  PubMed  Google Scholar 

  96. 96.

    Duréault A, Tcherakian C, Poiree S, Catherinot E, Danion F, Jouvion G, et al. Spectrum of pulmonary aspergillosis in Hyper IgE syndrome with autosomal dominant STAT3 deficiency. J Allergy Clin Immunol Pract.

  97. 97.

    Saijo T, Chen J, Chen SCA, Rosen LB, Yi J, Sorrell TC, et al. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. mBio. 2014;5:e00912–14.

    PubMed  PubMed Central  Google Scholar 

  98. 98.

    Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S, Shaw PA, et al. Adult-onset immunodeficiency in Thailand and Taiwan. New Engl J Med. 2012;367:725–34.

    CAS  PubMed  Google Scholar 

  99. 99.

    Lanternier F, Pathan S, Vincent QB, Liu L, Cypowyj S, Prando C, et al. Deep dermatophytosis and Inherited CARD9 deficiency. New Engl J Med. 2013;369:1704–14.

    CAS  PubMed  Google Scholar 

  100. 100.

    Corvilain E, Casanova J-L, Puel A. Inherited CARD9 Deficiency: Invasive disease caused by ascomycete fungi in previously healthy children and adults. J Clin Immunol. 2018;38:656–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Li J, Vinh DC, Casanova J-L, Puel A. Inborn errors of immunity underlying fungal diseases in otherwise healthy individuals. Curr Opin Microbiol. 2017;40:46–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, et al. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. New Engl J Med. 2014;370:421–32.

    CAS  PubMed  Google Scholar 

  103. 103.

    Rosselet A, Müllhaupt B, Laesser B, Ziegler CP, Benden C, Garzoni C, et al. PTX3 Polymorphisms and invasive mold infections after solid organ transplant. Clin Infect Dis. 2015;61:619–22.

    Google Scholar 

  104. 104.

    Hamon MA, Quintin J. Innate immune memory in mammals. Semin Immunol. 2016;28:351–8.

    CAS  PubMed  Google Scholar 

  105. 105.

    Milutinović B, Kurtz J. Immune memory in invertebrates. Semin Immunol. 2016;28:328–42.

    PubMed  Google Scholar 

  106. 106.

    Netea Mihai G, Quintin J, van der Meer Jos WM. Trained Immunity: a memory for innate host defense. Cell Host Microbe. 2011;9:355–61.

    CAS  PubMed  Google Scholar 

  107. 107.

    Fungi in Extreme Environments. In: Kubicek CP, Druzhinina IS, (eds). Environmental and Microbial Relationships. Berlin, Heidelberg: Springer Berlin Heidelberg; 2007. p. 85–103.

  108. 108.

    Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012;12:223–32.

    CAS  PubMed  Google Scholar 

  109. 109.

    Bekkering S, Blok BA, Joosten LAB, Riksen NP, van Crevel R, Netea MG. In vitro experimental model of trained innate immunity in human primary monocytes. Clin Vaccin Immunol: Cvi. 2016;23:926–33.

    CAS  Google Scholar 

  110. 110.

    Yoshida K, Maekawa T, Zhu Y, Renard-Guillet C, Chatton B, Inoue K, et al. The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. Nat Immunol. 2015;16:1034.

    CAS  PubMed  Google Scholar 

  111. 111.

    Saeed S, Quintin J, Kerstens HHD, Rao NA, Aghajanirefah A, Matarese F, et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Sci (New Y, NY). 2014;345:1251086.

    Google Scholar 

  112. 112.

    Cheng S-C, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Sci (New Y, NY). 2014;345:1250684.

    Google Scholar 

  113. 113.

    Arts RJW, Novakovic B, Ter Horst R, Carvalho A, Bekkering S, Lachmandas E, et al. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab. 2016;24:807–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Bekkering S, Arts RJW, Novakovic B, Kourtzelis I, van der Heijden CDCC, Li Y, et al. Metabolic Induction of Trained Immunity through the Mevalonate Pathway. Cell. 2018;172:135–46.e9.

    CAS  PubMed  Google Scholar 

  115. 115.

    Mitroulis I, Ruppova K, Wang B, Chen L-S, Grzybek M, Grinenko T, et al. Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell. 2018;172:147–61.e12.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Egerton-Warburton LM, Querejeta JI, Allen MF, Finkelman SL. Mycorrhizal Fungi. Reference Module in Earth Systems and Environmental Sciences: Elsevier; 2013.

  117. 117.

    Spribille T, Tuovinen V, Resl P, Vanderpool D, Wolinski H, Aime MC, et al. Basidiomycete yeasts in the cortex of ascomycete macrolichens. Science. 2016;353:488.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Grantham NS, Reich BJ, Pacifici K, Laber EB, Menninger HL, Henley JB, et al. Fungi identify the geographic origin of dust samples. PLoS One. 2015;10:e0122605.

    PubMed  PubMed Central  Google Scholar 

  119. 119.

    Richard ML, Sokol H The gut mycobiota: insights into analysis, environmental interactions and role in gastrointestinal diseases. Nature Reviews Gastroenterology & Hepatology. 2019.

  120. 120.

    Underhill DM, Iliev ID. The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol. 2014;14:405–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. 121.

    Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Sci (New Y, NY). 2012;336:1314–7.

    CAS  Google Scholar 

  122. 122.

    Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, Wu GD, et al. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One. 2013;8:e66019–e.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123.

    van Leeuwen PT, van der Peet JM, Bikker FJ, Hoogenkamp MA, Oliveira Paiva AM, Kostidis S, et al. Interspecies Interactions between Clostridium difficile and Candida albicans. mSphere. 2016;1:e00187–16.

    PubMed  PubMed Central  Google Scholar 

  124. 124.

    Briard B, Bomme P, Lechner BE, Mislin GLA, Lair V, Prévost M-C, et al. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci Rep. 2015;5:8220.

    PubMed  PubMed Central  Google Scholar 

  125. 125.

    Briard B, Heddergott C, Latgé J-P. Volatile compounds emitted by pseudomonas aeruginosa stimulate growth of the fungal pathogen aspergillus fumigatus. mBio. 2016;7:e00219–e.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. 126.

    Wheeler Matthew L, Limon Jose J, Bar Agnieszka S, Leal Christian A, Gargus M, Tang J, et al. Immunological consequences of intestinal fungal dysbiosis. Cell Host Microbe. 2016;19:865–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. 127.

    Beaudoin M, Goyette P, Boucher G, Lo KS, Rivas MA, Stevens C, et al. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis. PLoS Genet. 2013;9:e1003723.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet. 2011;43:1066–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    de Vries HS, Plantinga TS, van Krieken JH, Stienstra R, van Bodegraven AA, Festen EAM, et al. Genetic association analysis of the functional c.714T>G polymorphism and mucosal expression of Dectin-1 in inflammatory bowel disease. PLoS One. 2009;4:e7818.

    PubMed  PubMed Central  Google Scholar 

  130. 130.

    Chehoud C, Albenberg LG, Judge C, Hoffmann C, Grunberg S, Bittinger K, et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:1948–56.

    PubMed  PubMed Central  Google Scholar 

  131. 131.

    Bacher P, Hohnstein T, Beerbaum E, Röcker M, Blango MG, Kaufmann S, et al. Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell. 2019;176:1340–55.e15.

    CAS  PubMed  Google Scholar 

  132. 132.

    Koehler FC, Cornely OA, Wisplinghoff H, Schauss AC, Salmanton-Garcia J, Ostermann H, et al. Candida-reactive t cells for the diagnosis of invasive candida infection-A prospective pilot study. Front Microbiol. 2018;9:1381.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Guilhem Janbon.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Janbon, G., Quintin, J., Lanternier, F. et al. Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches. Genes Immun 20, 403–414 (2019). https://doi.org/10.1038/s41435-019-0071-2

Download citation

Further reading

Search

Quick links