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Genetic Diversity of Human Fungal Pathogens

  • MYCOLOGY (B BARKER, SECTION EDITOR)
  • Published:
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Abstract

Purpose of Review

Fungi represent a central yet often overlooked domain of clinically relevant pathogens that have become increasingly important in human disease. With unique adaptive lifestyles that vary widely across species, human fungal pathogens show remarkable diversity in their virulence strategies. The majority of these fungal pathogens are opportunistic, primarily existing in the environment or as commensals that take advantage of immunocompromised hosts to cause disease. In addition, many fungal pathogens have evolved from non-pathogenic lifestyles. The extent of genetic diversity and heritability of virulence traits remains poorly explored in human fungal pathogens.

Recent Findings

Genetic variation caused by mutations, genomic rearrangements, gene gain or loss, changes in ploidy, and sexual reproduction have profound effects on genetic diversity. These mechanisms contribute to the remarkable diversity of fungal genomes and have large impacts on their prevalence in human disease, virulence, and resistance to antifungal therapies.

Summary

Here, we focus on the genomic structure of the most common human fungal pathogens and the aspects of genetic variability that contribute to their dominance in human disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. O’Brien HE, Parrent JL, Jackson JA, Moncalvo J-M, Vilgalys R. Fungal community analysis by large-scale sequencing of environmental samples. Appl Environ Microbiol. 2005;71:5544–50.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rokas A. Evolution of the human pathogenic lifestyle in fungi. Nat Microbiol. 2022;7:607–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kainz K, Bauer MA, Madeo F, Carmona-Gutierrez D. Fungal infections in humans: the silent crisis. Microb Cell. 2020;7:143–5.

    Article  PubMed  PubMed Central  Google Scholar 

  4. WHO fungal priority pathogens list to guide research, development and public health action. Geneva: World Health Organization. 2022. Licence: CC BY-NC-SA 3.0 IGO.

  5. Hokken MWJ, Zwaan BJ, Melchers WJG, Verweij PE. Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi. Fungal Genet Biol. 2019;132:103254.

    Article  CAS  PubMed  Google Scholar 

  6. Taylor JW, Branco S, Gao C, Hann-Soden C, Montoya L, Sylvain I, et al. Sources of fungal genetic variation and associating it with phenotypic diversity. Microbiol Spectr. 2017;5(5). https://doi.org/10.1128/microbiolspec.FUNK-0057-2016.

  7. • Gibbons JG, Rokas A. The function and evolution of the Aspergillus genome. Trends Microbiol. 2013;21:14–22. A comprehensive review of the evolutionary relationships between Aspergillus species and the genetic structure and content of the Aspergillus genome.

  8. Genome [Internet]. Bethesda (MD). National Library of Medicine (US), National Center for Biotechnology Information; 2004 - [cited 2023 Jan 4]. Available from: https://www.ncbi.nlm.nih.gov/data-hub/genome/?taxon=5052&reference_only=true

  9. Barnes PD, Marr KA. Aspergillosis: spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am. 2006;20:545–61.

    Article  PubMed  Google Scholar 

  10. Barber AE, Sae-Ong T, Kang K, Seelbinder B, Li J, Walther G, et al. Aspergillus fumigatus pan-genome analysis identifies genetic variants associated with human infection. Nat Microbiol. 2021;6:1526–36.

    Article  CAS  PubMed  Google Scholar 

  11. Horta MAC, Steenwyk JL, Mead ME, dos Santos LHB, Zhao S, Gibbons JG, et al. Examination of genome-wide ortholog variation in clinical and environmental isolates of the fungal pathogen Aspergillus fumigatus. mBio. 2022;13:e01519-22.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sewell TR, Zhu J, Rhodes J, Hagen F, Meis JF, Fisher MC, et al. Nonrandom distribution of azole resistance across the global population of Aspergillus fumigatus. mBio. 2019;10:e00392-19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. • Bowyer P, Currin A, Delneri D, Fraczek MG. Telomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus. Nat Commun. 2022;13:5394. A recent study generating a high-quality telomere-to-telomere assembly of Aspergillus fumigatus.

  14. Etienne KA, Berkow EL, Gade L, Nunnally N, Lockhart SR, Beer K, et al. Genomic Diversity of Azole-Resistant Aspergillus fumigatus in the United States. mBio. 2021;12:e01803-21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mosquera J, Warn PA, Morrissey J, Moore CB, Gil-Lamaignere C, Denning DW. Susceptibility testing of Aspergillus flavus : Inoculum dependence with Itraconazole and lack of correlation between susceptibility to Amphotericin B in vitro and outcome in vivo. Antimicrob Agents Chemother. 2001;45:1456–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rudramurthy SM, Paul RA, Chakrabarti A, Mouton JW, Meis JF. Invasive Aspergillosis by Aspergillus flavus: epidemiology, diagnosis, antifungal resistance, and management. J Fungi. 2019;5:55.

    Article  CAS  Google Scholar 

  17. Drott MT, Satterlee TR, Skerker JM, Pfannenstiel BT, Glass NL, Keller NP, et al. The frequency of sex: population genomics reveals differences in recombination and population structure of the aflatoxin-producing fungus Aspergillus flavus. mBio. 2020;11:e00963-20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nierman WC, Yu J, Fedorova-Abrams ND, Losada L, Cleveland TE, Bhatnagar D, et al. Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes aflatoxin contamination of food and feed. Genome Announc. 2015;3:e00168-e215.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Gilbert MK, Mack BM, Moore GG, Downey DL, Lebar MD, Joardar V, et al. Whole genome comparison of Aspergillus flavus L-morphotype strain NRRL 3357 (type) and S-morphotype strain AF70. PLoS One. 2018;13:e0199169.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Fountain JC, Clevenger JP, Nadon B, Youngblood RC, Korani W, Chang P-K, et al. Two new Aspergillus flavus reference genomes reveal a large insertion potentially contributing to isolate stress tolerance and aflatoxin production. G3 GenesGenomesGenetics. 2020;10:3515–31.

    Article  CAS  Google Scholar 

  21. • Skerker JM, Pianalto KM, Mondo SJ, Yang K, Arkin AP, Keller NP, et al. Chromosome assembled and annotated genome sequence of Aspergillus flavus NRRL 3357. G3 GenesGenomesGenetics. 2021;11:jkab213. A recent study generating a near complete telomere-to-telomere assembly of Aspergillus flavus.

  22. Payne GA, Nierman WC, Wortman JR, Pritchard BL, Brown D, Dean RA, et al. Whole genome comparison of Aspergillus flavus and A. oryzae. Med Mycol. 2006;44:9–11.

    Article  Google Scholar 

  23. Wang P, Xu J, Chang PK, Liu Z, Kong Q. New insights of transcriptional regulator AflR in Aspergillus flavus physiology. Microbiol Spectr. 2022;10:e0079121.

    Article  PubMed  Google Scholar 

  24. Levitz SM. The Ecology of Cryptococcus neoformans and the Epidemiology of Cryptococcosis. Rev Infect Dis. 1991;13:1163–9.

    Article  CAS  PubMed  Google Scholar 

  25. Gillece JD, Schupp JM, Balajee SA, Harris J, Pearson T, Yan Y, et al. Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity. PLoS One. 2011;6:e28550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fu C, Davy A, Holmes S, Sun S, Yadav V, Gusa A, et al. Dynamic genome plasticity during unisexual reproduction in the human fungal pathogen Cryptococcus deneoformans. PLoS Genet. 2021;17(11). e1009935. https://doi.org/10.1371/journal.pgen.1009935.

  27. Samarasinghe H, Xu J. Hybrids and hybridization in the Cryptococcus neoformans and Cryptococcus gattii species complexes. Infect Genet Evol. 2018;66:245–55.

    Article  CAS  PubMed  Google Scholar 

  28. • Muñoz M, Camargo M, Ramírez JD. Estimating the intra-taxa diversity, population genetic structure, and evolutionary pathways of Cryptococcus neoformans and Cryptococcus gattii. Front Genet. 2018;9:148. A study that carried out extensive analysis of cryptococcal housekeeping genes that determined the phylogenetic relationships and evolutionary patterns of Cryptococcus neoformans and Cryptococcus gattii.

  29. Gusa A, Williams JD, Cho J-E, Averette AF, Sun S, Shouse EM, et al. Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro. Proc Natl Acad Sci. 2020;117:9973–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Janbon G, Ormerod KL, Paulet D, Byrnes EJ, Yadav V, Chatterjee G, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sephton-Clark P, McConnell SA, Grossman N, et al. Human and murine Cryptococcus neoformans infection selects for common genomic changes in an environmental isolate. bioRxiv; 2022. https://doi.org/10.1101/2022.04.12.487930.

  32. • Loftus BJ, Fung E, Roncaglia P, Rowley D, Amedeo P, Bruno D, et al. The genome of the Basidiomycetous yeast and human pathogen Cryptococcus neoformans. Science. 2005;307:1321–4. The first study to sequence the Cryptococcus genome.

  33. • Cuomo CA, Rhodes J, Desjardins CA. Advances in Cryptococcus genomics: insights into the evolution of pathogenesis. Mem Inst Oswaldo Cruz. 2018;113. A review focusing on the first genome-wide association studies detailing genetic variation related to virulence and microevolution between Cryptococcus isolates.

  34. Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ, Chrétien F, et al. Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathog. 2010;6:e1000953.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sephton-Clark P, Tenor JL, Toffaletti DL, Meyers N, Giamberardino C, Molloy SF, et al 2022 Genomic variation across a clinical Cryptococcus population linked to disease outcome. mBio e02626–22.

  36. D’Souza CA, Kronstad JW, Taylor G, Warren R, Yuen M, Hu G, et al. Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts. mBio. 2011;2:e00342-10.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Farrer RA, Desjardins CA, Sakthikumar S, Gujja S, Saif S, Zeng Q, et al. Genome evolution and innovation across the four major lineages of Cryptococcus gattii. mBio. 2015;6:e00868-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Turner SA, Butler G. The Candida Pathogenic Species Complex. Cold Spring Harb Perspect Med. 2014;4:a019778–a019778.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, Tullio V, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol. 2010;48:1366–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ernst JF. Transcription factors in Candida albicans—environmental control of morphogenesis. Microbiology (Reading). 2000;146( Pt 8):1763–74. https://doi.org/10.1099/00221287-146-8-1763.

  41. Merseguel KB, Nishikaku AS, Rodrigues AM, Padovan AC, e Ferreira RC, de Azevedo Salles MA, et al. Genetic diversity of medically important and emerging Candida species causing invasive infection. BMC Infect Dis. 2015;15:57.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Netea MG, Brown GD. Fungal infections: the next challenge. Curr Opin Microbiol. 2012;15:403–5.

    Article  PubMed  Google Scholar 

  43. Tavanti A, Davidson AD, Fordyce MJ, Gow NAR, Maiden MCJ, Odds FC. Population structure and properties of Candida albicans, as determined by multilocus sequence typing. J Clin Microbiol. 2005;43:5601–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Santos MAS, Tuite MF. The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res. 1995;23:1481–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 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. 2004;101:7329–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. van het Hoog M, Rast TJ, Martchenko M, Grindle S, Dignard D, Hogues H, et al. Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes. Genome Biol. 2007;8:R52.

    Article  Google Scholar 

  47. Muzzey D, Schwartz K, Weissman JS, Sherlock G. Assembly of a phased diploid Candida albicans genome facilitates allele-specific measurements and provides a simple model for repeat and indel structure. Genome Biol. 2013;14:R97.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Panthee S, Hamamoto H, Ishijima SA, Paudel A, Sekimizu K. Utilization of hybrid assembly approach to determine the genome of an opportunistic pathogenic fungus, Candida albicans TIMM 1768. Genome Biol Evol. 2018;10:2017–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hamlin J, Dias G, Bergman C, Bensasson D. Phased diploid genome assemblies for three strains of Candida albicans from Oak Trees. G3 (Bethesda). 2019;9:3574–3554.

    Article  Google Scholar 

  50. • Hickman MA, Paulson C, Dudley A, Berman J. Parasexual ploidy reduction drives population heterogeneity through random and transient aneuploidy in Candida albicans. Genetics. 2015;200:781–94. An elegant study illustrating that parasexual mating in Candida albicans results in tetraploidy and drives population heterogeneity, an important factor for maintaining genetic variation.

  51. Ene IV, Bennett RJ, Anderson MZ. Mechanisms of genome evolution in Candida albicans. Curr Opin Microbiol. 2019;52:47–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Berman J, Sudbery PE. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet. 2002;3:918–31.

    Article  CAS  PubMed  Google Scholar 

  53. • Selmecki A, Forche A, Berman J. Genomic plasticity of the human fungal pathogen Candida albicans. Eukaryot Cell. 2010;9:991–1008. An extensive review of the methods used for assessing genomic changes and the effect of stressors on large-scale genomic rearrangements in Candida albicans.

  54. Wang JM, Bennett RJ, Anderson MZ. The genome of the human pathogen Candida albicans Is shaped by mutation and cryptic sexual recombination. mBio. 2018;9:e01205-18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Harrison BD, Hashemi J, Bibi M, Pulver R, Bavli D, Nahmias Y, et al. A tetraploid intermediate precedes aneuploid formation in yeasts exposed to Fluconazole. PLoS Biol. 2014;12:e1001815.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ford CB, Funt JM, Abbey D, Issi L, Guiducci C, Martinez DA, et al. The evolution of drug resistance in clinical isolates of Candida albicans. eLife. 2015;4:e00662 eLife Sciences Publications, Ltd.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Selmecki A, Bergmann S, Berman J. Comparative genome hybridization reveals widespread aneuploidy in Candida albicans laboratory strains. Mol Microbiol. 2005;55:1553–65.

    Article  CAS  PubMed  Google Scholar 

  58. Bennett RJ. The parasexual lifestyle of Candida albicans. Curr Opin Microbiol. 2015;28:10–7.

    Article  PubMed  PubMed Central  Google Scholar 

  59. • Alby K, Schaefer D, Bennett RJ. Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature. 2009;460:890–3. The first report of homothallic (same-sex) mating in Candida albicans.

  60. Hickman MA, Zeng G, Forche A, Hirakawa MP, Abbey D, Harrison BD, et al. The ‘obligate diploid’ Candida albicans forms mating-competent haploids. Nature. 2013;494:55–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bennett R. Completion of a parasexual cycle in Candida albicans by induced chromosome loss in tetraploid strains. EMBO J. 2003;22:2505–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fidel PL, Vazquez JA, Sobel JD. Candida glabrata : review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev. 1999;12:80–96.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Diekema DJ, Messer SA, Brueggemann AB, Coffman SL, Doern GV, Herwaldt LA, et al. Epidemiology of Candidemia: 3-year results from the emerging infections and the epidemiology of Iowa Organisms Study. J Clin Microbiol. 2002;40:1298–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, et al. Genome evolution in yeasts. Nature. 2004;430(6995):35–44. https://doi.org/10.1038/nature02579.

  65. • Xu Z, Green B, Benoit N, Schatz M, Wheelan S, Cormack B. De novo genome assembly of Candida glabrata reveals cell wall protein complement and structure of dispersed tandem repeat arrays. Mol Microbiol. 2020;113:1209–24. A telomere-to-telomere assembly of the Candida glabrata genome, correcting errors in the tandem repeat regions of previous assemblies and improving assembly of the GPI-anchored cell wall proteins.

  66. Ahmad KM, Kokošar J, Guo X, Gu Z, Ishchuk OP, Piškur J. Genome structure and dynamics of the yeast pathogen Candida glabrata. FEMS Yeast Res. 2014;14:529–35.

    Article  CAS  PubMed  Google Scholar 

  67. Marcet-Houben M, Alvarado M, Ksiezopolska E, Saus E, de Groot PWJ, Gabaldón T. Chromosome-level assemblies from diverse clades reveal limited structural and gene content variation in the genome of Candida glabrata. BMC Biol. 2022;20:226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Guo X, Zhang R, Li Y, Wang Z, Ishchuk OP, Ahmad KM, et al. Understand the genomic diversity and evolution of fungal pathogen Candida glabrata by genome-wide analysis of genetic variations. Methods. 2020;176:82–90.

    Article  CAS  PubMed  Google Scholar 

  69. Zuza-Alves DL, Silva-Rocha WP, Chaves GM. An update on Candida tropicalis based on basic and clinical approaches. Front Microbiol. 2017;8:1927.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Keighley C, Gall M, van Hal SJ, Halliday CL, Chai LYA, Chew KL, et al. Whole genome sequencing shows genetic diversity, as well as clonal complex and gene polymorphisms associated with Fluconazole non-susceptible isolates of Candida tropicalis. J Fungi. 2022;8:896.

    Article  CAS  Google Scholar 

  71. • Butler G, Rasmussen MD, Lin MF, Santos MAS, Sakthikumar S, Munro CA, et al. Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature. 2009;459:657–62. This study generated genome sequences for six Candida species and carried out a comprehensive whole genome comparison between eight Candida species, identifying new genes.

  72. Doi M, Homma M, Chindamporn A, Tanaka K. Estimation of chromosome number and size by pulsed-field gel electrophoresis (PFGE) in medically important Candida species. J Gen Microbiol. 1992;138:2243–51.

    Article  CAS  PubMed  Google Scholar 

  73. Seervai RNH, Jones SK, Hirakawa MP, Porman AM, Bennett RJ. Parasexuality and ploidy change in Candida tropicalis. Eukaryot Cell. 2013;12:1629–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ola M, O’Brien CE, Coughlan AY, Ma Q, Donovan PD, Wolfe KH, et al. Polymorphic centromere locations in the pathogenic yeast Candida parapsilosis. Genome Res. 2020;30:684–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Logue ME, Wong S, Wolfe KH, Butler G. A Genome Sequence Survey Shows That The Pathogenic yeast Candida parapsilosis has a defective MTLa 1 allele at its mating type locus. Eukaryot Cell. 2005;4:1009–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tavanti A, Davidson AD, Gow NAR, Maiden MCJ, Odds FC. Candida orthopsilosis and Candida metapsilosis spp. Nov. To Replace Candida parapsilosis Groups II and III. J Clin Microbiol. 2005;43:284–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pryszcz LP, Németh T, Gácser A, Gabaldón T. Genome comparison of Candida orthopsilosis clinical strains reveals the existence of hybrids between two distinct subspecies. Genome Biol Evol. 2014;6:1069–78.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Riccombeni A, Vidanes G, Proux-Wéra E, Wolfe KH, Butler G. Sequence and analysis of the genome of the pathogenic yeast Candida orthopsilosis. PLoS One. 2012;7:e35750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gong J, Xiao M, Wang H, Kudinha T, Wang Y, Zhao F, et al. Genetic differentiation, diversity, and drug susceptibility of Candida krusei. Front Microbiol. 2018;9:2717.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Chan GF, Gan HM, Ling HL, Rashid NAA. Genome sequence of Pichia kudriavzevii M12, a potential producer of bioethanol and phytase. Eukaryot Cell. 2012;11:1300–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cuomo CA, Shea T, Yang B, Rao R, Forchie A. WHOLE GENOME SEQUENCE OF THE HETEROZYGOUS CLINICAL ISOLATE Candida krusei 81-B-5. G3 GenesGenomesGenetics. 2017;7:2883–9.

    Article  CAS  Google Scholar 

  82. Rhodes J, Fisher MC. Global epidemiology of emerging Candida auris. Curr Opin Microbiol. 2019;52:84–9.

    Article  PubMed  Google Scholar 

  83. Chow NA, Muñoz JF, Gade L, Berkow EL, Li X, Welsh RM, et al. Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. mBio. 2020;11:e03364-19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. • Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:134–40. A whole genome sequencing comparison between different Candida auris hospital isolates suggests a recent and near simultaneous emergence of clonal populations of C. auris on independent continents with varying levels of antifungal resistance.

  85. Spruijtenburg B, Badali H, Abastabar M, Mirhendi H, Khodavaisy S, Sharifisooraki J, et al. Confirmation of fifth Candida auris clade by whole genome sequencing. Emerg Microbes Infect. 2022;11:2405–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. • Muñoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, et al. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun. 2018;9:5346. Genome comparisons between Candida auris clades and closely related species identified chromosomal rearrangements and expanded gene families with functions in drug resistance and virulence.

  87. Bravo Ruiz G, Ross ZK, Holmes E, Schelenz S, Gow NAR, Lorenz A. Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates. Curr Genet. 2019;65:1217–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chakrabarti A, Singh S. Multidrug-resistant Candida auris : an epidemiological review. Expert Rev Anti Infect Ther. 2020;18:551–62.

    Article  CAS  PubMed  Google Scholar 

  89. Brown GD, Denning DW, Gow NAR, Levitz SM, Netea MG, White TC. Hidden killers: human fungal infections. Sci Transl Med. 2012;4:165rv13.

    Article  PubMed  Google Scholar 

  90. Sil A, Andrianopoulos A. Thermally dimorphic human fungal pathogens—polyphyletic pathogens with a convergent pathogenicity trait. Cold Spring Harb Perspect Med. 2015;5:a019794.

    Article  PubMed Central  Google Scholar 

  91. Ajello L. Comparative Morphology and Immunology of Members of the Genus Histoplasma: A review. Mycoses. 1968;11:507–14.

    Article  CAS  Google Scholar 

  92. Deepe GS. Outbreaks of histoplasmosis: The spores set sail. PLOS Pathog. 2018;14:e1007213.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Kasuga T, White TJ, Koenig G, Mcewen J, Restrepo A, Castañeda E, et al. Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol. 2003;12:3383–401.

    Article  CAS  PubMed  Google Scholar 

  94. Kasuga T, Taylor JW, White TJ. Phylogenetic relationships of varieties and geographical groups of the human pathogenic fungus Histoplasma capsulatum darling. J Clin Microbiol. 1999;37:653–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Jofre GI, Singh A, Mavengere H, Sundar G, D’Agostino E, Chowdhary A, et al. An Indian lineage of Histoplasma with strong signatures of differentiation and selection. Fungal Genet Biol. 2022;158:103654.

    Article  CAS  PubMed  Google Scholar 

  96. de Teixeira MM, Patané JSL, Taylor ML, Gómez BL, Theodoro RC, de Hoog S, et al. Worldwide phylogenetic distributions and population dynamics of the genus Histoplasma. PLoS Negl Trop Dis. 2016;10:e0004732.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Sepúlveda VE, Márquez R, Turissini DA, Goldman WE, Matute DR. Genome sequences reveal cryptic speciation in the human pathogen Histoplasma capsulatum. mBio. 2017;8:e01339-17.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Maxwell CS, Sepúlveda VE, Turissini DA, Goldman WE, Matute DR. Recent admixture between species of the fungal pathogen Histoplasma. Evol Lett. 2018;2:210–20.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Almeida-Silva F, de Melo TM, Matute DR, de Faria FM, Barker BM, Almeida-Paes R, et al. Genomic diversity analysis reveals a strong population structure in Histoplasma capsulatum LAmA (Histoplasma suramericanum). J Fungi. 2021;7:865.

    Article  CAS  Google Scholar 

  100. Canteros CE, Zuiani MF, Ritacco V, Perrotta DE, Reyes-Montes MR, Granados J, et al. Electrophoresis karyotype and chromosome-length polymorphism of Histoplasma capsulatum clinical isolates from Latin America. FEMS Immunol Med Microbiol. 2005;45:423–8.

    Article  CAS  PubMed  Google Scholar 

  101. Magrini V, Warren WC, Wallis J, Goldman WE, Xu J, Mardis ER, et al. Fosmid-based physical mapping of the Histoplasma capsulatum genome. Genome Res. 2004;14:1603–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. • Voorhies M, Cohen S, Shea TP, Petrus S, Muñoz JF, Poplawski S, et al. Chromosome-level genome assembly of a human fungal pathogen reveals synteny among geographically distinct species. 2022;13:12. A recent study that resequenced five Histoplasma strains and generated chromosomal assemblies.

  103. Jackson KM, Pelletier KC, Scheftel J, Kerkaert JD, Robinson SL, McDonald T, et al. Blastomyces dermatitidis environmental prevalence in Minnesota: analysis and modeling using soil collected at basal and outbreak sites. Appl Environ Microbiol. 2021;87:e01922-e2020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Brown EM, McTaggart LR, Zhang SX, Low DE, Stevens DA, Richardson SE. Phylogenetic analysis reveals a cryptic species Blastomyces gilchristii, sp. nov0 within the human pathogenic fungus Blastomyces dermatitidis. PLoS One. 2013;8:e59237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Muñoz JF, Gauthier GM, Desjardins CA, Gallo JE, Holder J, Sullivan TD, et al. The dynamic genome and transcriptome of the human fungal pathogen Blastomyces and close relative Emmonsia. PLOS Genet. 2015;11:e1005493.

    Article  PubMed  PubMed Central  Google Scholar 

  106. de Carvalho JA, Beale MA, Hagen F, Fisher MC, Kano R, Bonifaz A, et al. Exploring genetic diversity, population structure, and phylogeography in Paracoccidioides species using AFLP markers. Stud Mycol. 2021;100:100129–100129.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Desjardins CA, Champion MD, Holder JW, Muszewska A, Goldberg J, Bailão AM, et al. Comparative genomic analysis of human fungal pathogens causing Paracoccidioidomycosis. PLoS Genet. 2011;7:e1002345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mavengere H, Mattox K, Teixeira MM, Sepúlveda VE, Gomez OM, Hernandez O, McEwen J, Matute DR. Paracoccidioides Genomes reflect high levels of species divergence and little interspecific gene flow. mBio. 11(6):e01999-20. https://doi.org/10.1128/mBio.01999-20.

  109. Muñoz JF, Gallo JE, Misas E, Priest M, Imamovic A, Young S, et al. Genome update of the dimorphic human pathogenic fungi causing Paracoccidioidomycosis. PLoS Negl Trop Dis. 2014;8:e3348.

    Article  PubMed  PubMed Central  Google Scholar 

  110. de Teixeira MM, Cattana ME, Matute DR, Muñoz JF, Arechavala A, Isbell K, et al. Genomic diversity of the human pathogen Paracoccidioides across the South American continent. Fungal Genet Biol. 2020;140:103395.

    Article  CAS  PubMed  Google Scholar 

  111. Muñoz JF, Farrer RA, Desjardins CA, Gallo JE, Sykes S, Sakthikumar S, et al. Genome diversity, recombination, and virulence across the major lineages of Paracoccidioides. mSphere. 2016;1:e00213-16.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Neafsey DE, Barker BM, Sharpton TJ, Stajich JE, Park DJ, Whiston E, et al. Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control. Genome Res. 2010;20:938–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Fisher MC, Koenig GL, White TJ, Taylor JW. Molecular and phenotypic description of Coccidioides posadasii sp. nov., previously recognized as the non-California population of Coccidioides immitis. Mycologia. 2002;94(1):73–84.

  114. • de Melo Teixeira M, Stajich JE, Sahl JW, Thompson GR, Brem RB, Dubin CA, et al. A chromosomal-level reference genome of the widely utilized Coccidioides posadasii laboratory strain “Silveira.” G3 GenesGenomesGenetics. 2022;12:jkac031. The most recent assembly of a Coccidioides genome.

  115. Maxwell CS, Mattox K, Turissini DA, Teixeira MM, Barker BM, Matute DR. Gene exchange between two divergent species of the fungal human pathogen, Coccidioides: Introgression between two fungal pathogens. Evolution. 2019;73:42–58.

    Article  PubMed  Google Scholar 

  116. Teixeira MM, Alvarado P, Roe CC, Thompson GR, Patané JSL, Sahl JW, et al. Population structure and genetic diversity among isolates of Coccidioidesposadasii in Venezuela and surrounding regions. mBio. 2019;10:e01976-19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Barker BM, Rajan S, De Melo TM, Sewnarine M, Roe C, Engelthaler DM, et al. Coccidioidal meningitis in New York traced to texas by fungal genomic analysis. Clin Infect Dis. 2019;69:1060–2.

    Article  PubMed  Google Scholar 

  118. Pappas PG, Tellez I, Deep AE, Nolasco D, Holgado W, Bustamante B. Sporotrichosis in Peru: description of an area of hyperendemicity. Clin Infect Dis. 2000;30:65–70.

    Article  CAS  PubMed  Google Scholar 

  119. • Teixeira MM, de Almeida LG, Kubitschek-Barreira P, Alves FL, Kioshima ÉS, Abadio AK, et al. Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis. BMC Genomics. 2014;15:943. A whole genome comparative study between Sporothrix schenckii and Sporothrix brasiliensis that identified an ecological shift from degrading plant-matter to mammalian parasitism with the loss of polysaccharide lyase genes and expansions in GTPases and PKS proteins.

  120. de Carvalho JA, Hagen F, Fisher MC, de Camargo ZP, Rodrigues AM. Genome-wide mapping using new AFLP markers to explore intraspecific variation among pathogenic Sporothrix species. PLoS Negl Trop Dis. 2020;14:e0008330.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Cuomo CA, Rodriguez-Del Valle N, Perez-Sanchez L, Abouelleil A, Goldberg J, Young S, et al. Genome sequence of the pathogenic fungus Sporothrix schenckii (ATCC 58251). Genome Announc. 2014;2:e00446-e514.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Giosa D, Felice MR, Giuffrè L, AieseCigliano R, Paytuví-Gallart A, Lo Passo C, et al. Transcriptome-wide expression profiling of Sporothrixschenckii yeast and mycelial forms and the establishment of the Sporothrix Genome DataBase. Microb Genomics. 2020;6:mgen000445.

    Article  Google Scholar 

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Acknowledgements

We thank members of the Beyhan lab and Dr. Matthew Martens for their comments on the manuscript.

Funding

SB is supported by the National Institutes of Health (R01AI137418 and U19AI166059), Centers for Disease Control and Prevention (U54CK000603) and the Office of Naval Research (N00014-20–1-2120).

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  1. Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA, 92037, USA

    Jillian Freese & Sinem Beyhan

  2. Department of Medicine, University of California, San Diego, San Diego, CA, 92093, USA

    Sinem Beyhan

  3. Infectious Diseases Section, VA Healthcare San Diego, San Diego, CA, 92161, USA

    Sinem Beyhan

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Freese, J., Beyhan, S. Genetic Diversity of Human Fungal Pathogens. Curr Clin Micro Rpt 10, 17–28 (2023). https://doi.org/10.1007/s40588-023-00188-4

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