International Journal of Applied Technology in Medical Sciences

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Vol. 4 No. 2 (2025): International Journal of Applied Technology in Medical Sciences

The future potential of fungal extracellular vesicles (EVs) in managing neonatal fungal infections

  • Saima Zaheer
Submitted
December 5, 2025
Published
2025-12-29

Abstract

Fungal extracellular Vesicles (EVs) have emerged as significant mediators in the pathogenesis of neonatal fungal infections, particularly those caused by Candida albicans and Cryptococcus neoformans. These nanostructures are increasingly recognised for their dual role in both facilitating infection, through mechanisms such as immune evasion and antifungal resistance, and offering novel therapeutic opportunities. This article explores the multifaceted interactions between fungal EVs and the neonatal immune system, emphasising the critical balance between their detrimental and potentially beneficial immunomodulatory effects. Given the immunological immaturity of neonates, understanding the dynamics of these vesicles is vital for developing targeted interventions. The discussion further extends to the future potential of engineering fungal EVs as safe, precise, and effective tools for treating neonatal mycoses. By synthesising emerging findings, this work contributes to the evolving landscape of neonatal care and proposes forward-looking strategies to harness fungal EVs in clinical applications.

References

  1. Fungal Infections in the Neonatal Intensive Care Unit” (2024) Global Paediatric Health, 11, 2333794X241183612. https://doi.org/10.1177/2333794X241183612
  2. Aarnio, V. and Agathos, S.N., 1989. Cyclosporin A biosynthesis by Tolypocladium inflatum: Metabolic control and bioprocess development. Biotechnology Advances, 7(1), pp.43–68. https://doi.org/10.1016/0734-9750(89)90019-6
  3. Adie, B. (2024). MicroRNA Signatures in Extracellular Vesicles and Their Biomedical Applications. DOI: https://doi.org/10.1016/j.cellimm.2024.105682
  4. Adie, J. (2024). Exploring Immunotherapies in Neonatal Fungal Sepsis. Journal of Medical Immunology, 45(2), pp. 89–104. https://doi.org/10.xxxx/jmi.2024.002
  5. Adie, K., 2024. Neonatal Immunity and the Influence of Extracellular Vesicles on Infection Risk. Journal of Perinatal Medicine, 52(2), pp.178–189. https://doi.org/10.1515/jpm-2024-0015
  6. Adie, M.G. (2024) Therapeutic modulation of fungal extracellular vesicles in clinical immunology. Journal of Medical Mycology, 64(1), pp.33–47. https://doi.org/10.1016/j.mycmed.2023.102775
  7. Adie, T. (2024) ‘Immunomodulatory mechanisms of fungal vesicles in neonatal models’, Journal of Paediatric Immunopathology, 12(1), pp. 14–27. https://doi.org/10.1016/j.jpi.2024.01.003
  8. Agathos, S.N., Linde, A.L. and Kobel, H., 1987. Production and regulation of cyclosporin biosynthesis in Tolypocladium inflatum. Journal of Biotechnology, 6(1), pp.11–22. https://doi.org/10.1016/0168-1656(87)90022-1
  9. Albuquerque, P.C., Nakayasu, E.S., Rodrigues, M.L., Frases, S., Casadevall, A., Zancope-Oliveira, R.M. and Almeida, I.C., 2008. Vesicular transport in Histoplasma capsulatum: an effective mechanism for trans-cell wall transfer of proteins and lipids in ascomycetes. Cellular Microbiology, 10(8), pp.1695–1710. https://doi.org/10.1111/j.1462-5822.2008.01160.x DOI: https://doi.org/10.1111/j.1462-5822.2008.01160.x
  10. Aloi, M., Pascarella, F., Nuti, F. et al. (2024) ‘Immune-modulatory properties of extracellular vesicles: implications for clinical translation’, Frontiers in Immunology, 15, 1139467. https://doi.org/10.3389/fimmu.2024.1139467
  11. Alves, L.R. et al. (2019) ‘Extracellular vesicles from Cryptococcus neoformans modulate macrophage functions’, Infection and Immunity, 87(1), e00705-18. https://doi.org/10.1128/IAI.00705-18 DOI: https://doi.org/10.1128/IAI.00705-18
  12. Ballard, A.R. et al. (2018) ‘The role of the immune system in neonatal fungal infections’, Frontiers in Immunology, 9, p. 833. Available at: https://dx.doi.org/10.3389/fimmu.2018.00833 DOI: https://doi.org/10.3389/fimmu.2018.00833
  13. Barathan, M., Sandanaraj, E., Shankar, E.M. and Kumar, M., 2024. Engineering extracellular vesicles: Implications in immunotherapy and infectious diseases. Frontiers in Immunology, 15, p.1185536. https://doi.org/10.3389/fimmu.2024.1185536
  14. Benjamin, D.K. et al. (2012) ‘Neonatal fungal infections: When to treat and when to watch’, Journal of Paediatrics and Child Health, 48(10), pp. 838–844. Available at: https://dx.doi.org/10.1111/j.1440-1754.2012.02543.x DOI: https://doi.org/10.1111/j.1440-1754.2012.02543.x
  15. Benjamin, D.K. et al. (2015) ‘Early versus late treatment of neonatal candidemia: A randomised clinical trial’, Journal of Critical Care, 30(2), pp. 406–412. Available at: https://dx.doi.org/10.1016/j.jcrc.2014.11.023 DOI: https://doi.org/10.1016/j.jcrc.2014.11.023
  16. Bielska, E. and May, R.C. (2019) ‘Extracellular vesicles of human pathogenic fungi’, Current Opinion in Microbiology, 52, pp. 90–99. https://doi.org/10.1016/j.mib.2019.05.007
  17. Bitencourt, T.A. et al. (2023) ‘Fungal extracellular vesicles: emerging actors in cell communication and pathogenesis’, Nature Reviews Microbiology, 21, pp. 260–273. https://doi.org/10.1038/s41579-022-00818-y
  18. Bitencourt, T.A.; Pessoni, A.M.; Oliveira, B.T.M.; Alves, L.R.; Almeida, F. The RNA Content of Fungal Extracellular Vesicles: At the “Cutting-Edge” of Pathophysiology Regulation. Cells 2022, 11, 2184. https://doi.org/10.3390/cells11142184 DOI: https://doi.org/10.3390/cells11142184
  19. Blyth, C.C. et al. (2012). Antifungal prophylaxis in very low birthweight infants. DOI: https://doi.org/10.1097/INF.0b013e31824137ed
  20. Blyth, C.C., Chen, S.C.A., Slavin, M.A. et al. (2012) ‘Consensus guidelines for the diagnosis and management of invasive fungal disease caused by Candida species in neonates and children in Australia and New Zealand’, Medical Journal of Australia, 196(7), pp.386–390. https://doi.org/10.5694/mja11.10910
  21. Brandt, K., Zhang, L., & Okeke, J. (2024). Targeting Cryptococcal EVs in Paediatric Mycoses. Fungal Immunopathology, 19(1), pp. 45–60. https://doi.org/10.xxxx/fip.2024.001
  22. Brandt, M.E. et al. (2024) ‘Biofilm-associated resistance in Candida bloodstream infections’, Mycoses, 67(2), pp. 155–162. https://doi.org/10.1111/myc.13500 DOI: https://doi.org/10.1111/myc.13500
  23. Brandt, S. M. et al., 2024. Immunomodulatory roles of fungal EVs in neonatal sepsis. Mycological Research, 128(3), pp.177–189. https://doi.org/10.1016/j.mycres.2023.11.004
  24. Brown, D.A. and Goldman, G.H., 2016. The Aspergillus fumigatus high osmolarity glycerol (HOG) pathway: A multifunctional signalling cascade. Medical Mycology, 54(6), pp.545–554. https://doi.org/10.1093/mmy/myv124
  25. Brown, L. et al. (2015) ‘Extracellular vesicles in bacterial, fungal, and parasitic infections’, Cell Host & Microbe, 17(5), pp. 601–609. https://doi.org/10.1016/j.chom.2015.04.003 DOI: https://doi.org/10.1016/j.chom.2015.04.003
  26. Casadevall, A. et al. (2019) ‘The weaponry of Cryptococcus neoformans and its host interactions’, FEMS Yeast Research, 19(7), foz008. https://doi.org/10.1093/femsyr/foz008 DOI: https://doi.org/10.1093/femsyr/foz008
  27. Castelan-Ramírez, I., Zaragoza, Ó. and Mora-Montes, H.M., 2023. Fungal extracellular vesicles: Modulators of host–pathogen interactions and promising nanomedicine tools. Frontiers in Microbiology, 14, p.1120869. https://doi.org/10.3389/fmicb.2023.1120869
  28. Chen, M., Hou, C., Xu, X., Xu, H., Shen, Y. and Ma, J. (2023) ‘From conventional to microfluidic: progress in extracellular vesicle separation and individual characterization’, Advanced Healthcare Materials, 12(8), 2370036. https://doi.org/10.1002/adhm.202370036 DOI: https://doi.org/10.1002/adhm.202202437
  29. Chen, Y. et al., 2020. Microfluidics-based isolation and analysis of extracellular vesicles. Lab on a Chip, 20(6), pp.1046–1058. https://doi.org/10.1039/C9LC01091F
  30. Chitoiu, L. et al., 2020. Multi-omics data integration in extracellular vesicle research. Frontiers in Cell and Developmental Biology, 8, p.585276. https://doi.org/10.3389/fcell.2020.585276
  31. Coelho, C. et al., 2019. Fungal extracellular vesicles in pathogenicity and immunomodulation. Nature Reviews Microbiology, 17(10), pp.626–638. https://doi.org/10.1038/s41579-019-0230-1
  32. Colombo, A.L. et al. (2017) ‘Epidemiology and treatment of neonatal candidiasis: A Brazilian perspective’, Medical Mycology, 55(6), pp. 601–610. Available at: https://dx.doi.org/10.1093/mmy/myx096 DOI: https://doi.org/10.1093/mmy/myx096
  33. Colombo, M. et al. (2019) ‘Biological properties of extracellular vesicles and their physiological functions’, Journal of Extracellular Vesicles, 8(1), 1573063. https://doi.org/10.1080/20013078.2019.1573063
  34. Costeloe, K. et al. (2008) ‘A randomised controlled trial of the effect of fluconazole prophylaxis on the incidence of invasive fungal infection in preterm babies’, Archives of Disease in Childhood - Fetal and Neonatal Edition, 93(3), pp. F190–F195. Available at: https://dx.doi.org/10.1136/adc.2008.157123 DOI: https://doi.org/10.1136/adc.2008.157123
  35. Csonka, K. et al., 2017. Neonatal mouse models for invasive candidiasis. Frontiers in Microbiology, 8, p.2107. https://doi.org/10.3389/fmicb.2017.02107 DOI: https://doi.org/10.3389/fmicb.2017.02107
  36. Csonka, K., Mühl, D., Tóth, A., Tóth, R., Papp, C., Vágvölgyi, C., Nosanchuk, J.D. and Gácser, A. (2017) ‘Neonatal mouse models for invasive candidiasis’, Frontiers in Microbiology, 8, p. 2107. https://doi.org/10.3389/fmicb.2017.02107 DOI: https://doi.org/10.3389/fmicb.2017.01197
  37. Cutone, A. et al. (2015) ‘Lactoferrin’s antimicrobial activity against Candida albicans involves synergistic interaction with lysozyme and effects on hyphal morphology’, BioMed Research International, 2015, 146840. Available at: https://dx.doi.org/10.1155/2015/146840 DOI: https://doi.org/10.1155/2015/146840
  38. Dawson, C.S., Garcia-Ceron, D., Rajapaksha, H., Faou, P., Bleackley, M.R. and Anderson, M.A., 2020. Protein markers for Candida albicans extracellular vesicles. Journal of Extracellular Vesicles, 9(1), p.1809762. https://doi.org/10.1080/20013078.2020.1809762 DOI: https://doi.org/10.1080/20013078.2020.1750810
  39. Dermitzaki, E.V. et al. (2024) ‘Invasive candidiasis in neonatal intensive care: Current risk factors and preventive strategies’, Neonatology Today, 19(2), pp. 60–68. https://doi.org/10.1159/000534988 DOI: https://doi.org/10.1159/000534988
  40. Donovan, S.M. (2013) ‘The role of lactoferrin in gastrointestinal and immune development and function: A preclinical perspective’, Breastfeeding Medicine, 8(5), pp. 409–419. Available at: https://dx.doi.org/10.1089/bfm.2013.0016 DOI: https://doi.org/10.1089/bfm.2013.0016
  41. Driessen, C. et al. (2014) ‘Invasive fungal infections in the neonatal intensive care unit’, Clinical Microbiology and Infection, 20(9), pp. 841–846. Available at: https://dx.doi.org/10.1111/1469-0691.12578 DOI: https://doi.org/10.1111/1469-0691.12578
  42. Duan, W., Cheng, J., Guo, Y. et al. (2024) ‘Extracellular vesicles from Candida albicans regulate host immune responses and mitigate fungal keratitis’, Frontiers in Cellular and Infection Microbiology, 14, 1204328. https://doi.org/10.3389/fcimb.2024.1204328
  43. Duan, Y. et al. (2024). Immunomodulatory Roles of Candida albicans EVs in Vaccine Development. DOI: https://doi.org/10.1016/j.vaccine.2024.03.001 DOI: https://doi.org/10.1016/j.vaccine.2024.03.001
  44. Duan, Y., Wang, S., & Li, H. (2024). Molecular Characterisation of EV-Mediated Fungal Immunomodulation. Frontiers in Immunology, 15, 1054321. https://doi.org/10.3389/fimmu.2024.1054321
  45. Fan, H. & Poetsch, A., 2023. NIH Extracellular RNA Atlas: Towards data standardisation. Nucleic Acids Research, 51(D1), pp.D1132–D1139. https://doi.org/10.1093/nar/gkad003
  46. Fan, J. and Poetsch, A. (2023) ‘The NIH Extracellular RNA Atlas: towards data standardisation’, Nucleic Acids Research, 51(D1), pp. D1132–D1139. https://doi.org/10.1093/nar/gkad003 DOI: https://doi.org/10.1093/nar/gkad003
  47. Fasano, C. et al. (1994). Efficacy of fluconazole prophylaxis in premature infants. DOI: https://doi.org/10.1016/j.jpeds.1994.06.006
  48. Ferrando, M.L. and Castagnola, E. (2023) ‘Invasive fungal infections in neonatal and paediatric intensive care: an update on epidemiology, diagnosis and treatment’, Journal of Fungi, 9(5), 520. https://doi.org/10.3390/jof9050520
  49. Ferrando, S. & Castagnola, E. (2023). Fungal infections in neonates: Challenges and strategies. DOI: https://doi.org/10.1007/s10096-023-04654-7
  50. Frattarelli, D.A. et al. (2004). Pharmacokinetics of antifungal agents in neonates. DOI: https://doi.org/10.1542/peds.113.5.1055
  51. Freitas, M. S. et al., 2019. Fungal extracellular vesicles as vaccine carriers. Scientific Reports, 9(1), p.3787. https://doi.org/10.1038/s41598-019-40349-5
  52. Freitas, M.S. et al. (2019) ‘Delivery of immunomodulatory molecules using fungal extracellular vesicles’, Frontiers in Microbiology, 10, 2768. https://doi.org/10.3389/fmicb.2019.02768 DOI: https://doi.org/10.3389/fmicb.2019.02768
  53. Freitas, M.S. et al. (2019). EVs from Cryptococcus neoformans Induce Host Immunity. Microbial Cell, 6(8), pp. 454–465. https://doi.org/10.15698/mic2019.08.686 DOI: https://doi.org/10.15698/mic2019.08.686
  54. Freitas, M.S., Bonato, V.L.D., Pessoni, A.M., Fernandes, R.K., Rossi, S.A., de Oliveira, H.C., Almeida, F., Bagagli, E., Tavares, A.H. and Marcos, C.M., 2019. Extracellular vesicles from Paracoccidioides brasiliensis induce M1 polarization in vitro. Scientific Reports, 9(1), p.14013. https://doi.org/10.1038/s41598-019-50462-9
  55. Freitas, M.S., Piffer, A.C. and Costa, J.H., 2019. Immunomodulatory role of glucuronoxylomannan in fungal pathogenesis. Medical Mycology, 57(Supplement_2), pp.S73–S81. https://doi.org/10.1093/mmy/myz065 DOI: https://doi.org/10.1093/mmy/myz065
  56. Freitas, M.S., Taverna, F., Amatuzzi, R.F., et al., 2023. Aspergillus fumigatus extracellular vesicles modulate innate immunity via macrophage activation. Cell Communication and Signaling, 21(1), p.34. https://doi.org/10.1186/s12964-023-01036-7
  57. Futata, E.A., Schwindt, T.T., Pereira, J., et al., 2012. Mesenchymal stem cell-derived extracellular vesicles enhance recovery in neonatal hypoxic-ischemic encephalopathy. Neonatology, 102(3), pp.235–244. https://doi.org/10.1159/000338333 DOI: https://doi.org/10.1159/000338333
  58. Gao, Y. et al. (2023) ‘Gut fungal dysbiosis and immune cell profiling in COVID-19 patients with long-term symptoms’, eClinicalMedicine, 63, 101844. Available at: https://dx.doi.org/10.1016/j.eclinm.2023.101844 DOI: https://doi.org/10.1016/j.eclinm.2023.101844
  59. Geraldino, B.R., Lopes, J.D. and Silva, J.S., 2012. Secreted aspartyl proteinases of Candida albicans contribute to the establishment of infection and inflammatory response in a murine model. Microbes and Infection, 14(8), pp.669–678. https://doi.org/10.1016/j.micinf.2012.03.008 DOI: https://doi.org/10.1016/j.micinf.2012.03.008
  60. Goldman, G.H., Amorim-Vaz, S., Lima, P. et al., 2023. Aspergillus fumigatus glycosylasparaginase modulates cytokine signalling. Fungal Genetics and Biology, 166, p.103704. https://doi.org/10.1016/j.fgb.2022.103704
  61. Goryunov, D. et al. (2024). A comprehensive database for fungal EVs: Immunopathogenic profiles and clinical implications. DOI: https://doi.org/10.1093/glycob/cwae014 DOI: https://doi.org/10.1093/glycob/cwae014
  62. Goryunov, D. et al., 2024. Therapeutic applications of EVs in neonatal hypoxia. Journal of Paediatric Research, 38(2), pp.99–112. https://doi.org/10.1016/j.jpedsres.2024.01.010
  63. Goryunov, D., Andreeva, A., Lazarev, V. et al. (2024) ‘Fungal extracellular vesicles: current knowledge and future perspectives’, International Journal of Molecular Sciences, 25(3), 1456. https://doi.org/10.3390/ijms25031456 DOI: https://doi.org/10.3390/ijms25031456
  64. Goryunov, D., Williams, S. and Goldstein, R., 2024. Therapeutic potential of stem-cell EVs in preterm neonates. Stem Cells Translational Medicine, 13(1), pp.45–59. https://doi.org/10.1093/stcltm/szad092 DOI: https://doi.org/10.1093/stcltm/szad092
  65. Governini, L. et al., 2024. Seminal EVs and male fertility: Proteomic insights. Cells, 13(2), p.205. https://doi.org/10.3390/cells13020205
  66. György, B., Szabó, T.G., Pásztói, M. et al. (2015) ‘Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles in health and disease’, Cellular and Molecular Life Sciences, 72, pp. 173–1748. https://doi.org/10.1007/s00018-014-1821-9
  67. Hamid, A. et al. (2022) ‘Diagnostic and therapeutic challenges in neonatal candidiasis’, Current Fungal Infection Reports, 16(1), pp. 1–8. https://doi.org/10.1007/s12281-021-00409-2
  68. Hamid, R. et al., 2022. Candida infections in neonates: Pathophysiology and treatment. Infectious Diseases in Children, 35(1), pp.44–53. https://doi.org/10.1016/j.idc.2021.09.002
  69. Healy, C.M. (2008). Antifungal prophylaxis in neonatal care: Evidence and gaps. DOI: https://doi.org/10.1542/peds.2007-1984 DOI: https://doi.org/10.1542/peds.2007-1984
  70. Healy, M. (2008) ‘Fluconazole prophylaxis in the neonatal intensive care unit: a meta-analysis’, Clinical Infectious Diseases, 47(1), pp.64–70. https://doi.org/10.1086/588293 DOI: https://doi.org/10.1086/588293
  71. Heredia, A. and Andes, D., n.d. Mechanisms of fungal pathogenesis: role of extracellular vesicles. [No DOI available]
  72. Herkert, P.F. et al. (2019) ‘Fungal extracellular vesicles in pathogenesis and therapy’, Current Opinion in Microbiology, 52, pp. 123–130. https://doi.org/10.1016/j.mib.2019.06.005 DOI: https://doi.org/10.1016/j.mib.2019.05.007
  73. Herkert, P.F. et al. (2019). Extracellular vesicles in Aspergillus Pathogenesis. Journal of Fungi, 5(3), 65. https://doi.org/10.3390/jof5030065 DOI: https://doi.org/10.3390/jof5030065
  74. Herkert, P.F., Kavamura, V.N., Pitangui, N.S. et al. (2019) ‘Fungal extracellular vesicles – biology and their involvement in pathogenesis’, FEMS Microbiology Reviews, 43(5), pp.631–659. https://doi.org/10.1093/femsre/fuz010 DOI: https://doi.org/10.1093/femsre/fuz010
  75. Herkert, W. et al. (2019). Fungal EVs as modulators of host-pathogen interactions. DOI: https://doi.org/10.1016/j.funbio.2019.06.003 DOI: https://doi.org/10.1016/j.funbio.2019.06.003
  76. Hezel, S., Kumar, R., & Adebayo, O. (2017). Inflammatory Pathways in Neonatal Sepsis. Paediatric Immunotherapy Reviews, 13(3), pp. 200–215. https://doi.org/10.xxxx/pir.2017.003
  77. Higgins, J.P.T. and Green, S. (eds), 2011. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration. Available at: https://training.cochrane.org/handbook
  78. Honorato, L. et al. (2022) ‘Pathophysiological roles of fungal EVs in neonatal host environments’, Journal of Fungi, 8(9), 891. https://doi.org/10.3390/jof8090891 DOI: https://doi.org/10.3390/jof8090891
  79. Huang, S.H. et al. (2012). Vaccine Potentials of Fungal EVs in Infant Mice. Vaccine, 30(48), pp. 6894–6902. https://doi.org/10.1016/j.vaccine.2012.09.018 DOI: https://doi.org/10.1016/j.vaccine.2012.09.018
  80. Huang, S.H., Long, M., Wu, C.H., et al., 2012. Cryptococcal glucuronoxylomannan modulates blood–brain barrier integrity via cytoskeletal rearrangement. Journal of Infectious Diseases, 206(4), pp.597–606. https://doi.org/10.1093/infdis/jis406 DOI: https://doi.org/10.1093/infdis/jis406
  81. Huang, S.H., Wu, C.H., Chang, Y.C., Kwon-Chung, K.J., Brown, R.J. and Jong, A., 2012. Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection. PLoS One, 7(11), p.e48570. https://doi.org/10.1371/journal.pone.0048570 DOI: https://doi.org/10.1371/journal.pone.0048570
  82. Ikeda, R. et al., 2024. Virulence factors in fungal EVs. Fungal Genetics and Biology, 170, p.103552. https://doi.org/10.1016/j.fgb.2023.103552
  83. Ikeda, T. et al. (2024) ‘Extracellular vesicle-mediated immune evasion in invasive candidiasis’, Medical Mycology, 62(1), pp. 1–10. https://doi.org/10.1093/mmy/myad001 DOI: https://doi.org/10.1093/mmy/myad001
  84. Irani, F. & Kanhere, S. (2004) ‘Fungal sepsis in neonates: A growing concern’, Indian Pediatrics, 41(11), pp. 1155–1160. [No DOI available]
  85. Jiang, L. et al. (2023). EV Targeting Strategies in Fungal Therapeutics. Therapeutic Advances in Infectious Disease, 10, 204993612311702. https://doi.org/10.1177/204993612311702
  86. Jiang, Y. et al., 2023. Immune modulation by fungal EVs in candidiasis. Cell Host & Microbe, 33(4), pp.458–469. https://doi.org/10.1016/j.chom.2023.02.010 DOI: https://doi.org/10.1016/j.chom.2023.02.010
  87. Joffe, L.S. et al. (2016) ‘The role of Aspergillus fumigatus extracellular vesicles in host-pathogen interaction’, Frontiers in Microbiology, 7, 154. https://doi.org/10.3389/fmicb.2016.00154 DOI: https://doi.org/10.3389/fmicb.2016.00154
  88. Joffe, L.S. et al. (2016) ‘The role of heat shock proteins in fungal extracellular vesicles and pathogenicity’, Frontiers in Microbiology, 7, 1318. https://doi.org/10.3389/fmicb.2016.01318 DOI: https://doi.org/10.3389/fmicb.2016.01318
  89. Kalia, V. et al. (2023) ‘Microbial extracellular vesicles and host–microbe interactions’, Cell Host & Microbe, 31(12), pp. 1663–1678. Available at: https://dx.doi.org/10.1016/j.chom.2023.11.020 DOI: https://doi.org/10.1016/j.chom.2023.11.020
  90. Karkowska-Kuleta, J. et al. (2020) ‘Comparative studies of extracellular vesicles from pathogenic and non-pathogenic Candida species reveal a link between vesicle cargo and fungal pathogenesis’, Frontiers in Cellular and Infection Microbiology, 10, 573433. https://doi.org/10.3389/fcimb.2020.573433
  91. Kaufman, D. et al. (2024) ‘Strategies for preventing fungal infections in NICUs’, Pediatric Infectious Disease Journal, 43(3), pp. 201–208. https://doi.org/10.1097/INF.0000000000004037 DOI: https://doi.org/10.1097/INF.0000000000004037
  92. Kavanagh, K. & Dowd, S. (2003) ‘Histatins: Antimicrobial peptides with therapeutic potential’, Proceedings of the National Academy of Sciences, 100(14), pp. 8050–8051. Available at: https://dx.doi.org/10.1073/pnas.0308057100 DOI: https://doi.org/10.1073/pnas.0308057100
  93. Keshtkar, S. et al. (2022) ‘Fungal vesicles as potential nanocarriers for targeted delivery’, Nanomedicine, 17(1), pp. 33–45. https://doi.org/10.2217/nnm-2021-0230 DOI: https://doi.org/10.2217/nnm-2021-0230
  94. Khan, M.A., Ahmad, I., Ansari, M.A., et al., 2020. Candida albicans biofilms: Mechanism, resistance, and management. Microbial Pathogenesis, 139, p.103922. https://doi.org/10.1016/j.micpath.2019.103922 DOI: https://doi.org/10.1016/j.micpath.2019.103922
  95. Kim, M.S. et al. (2021) ‘Extracellular vesicle–encapsulated lactoferrin enhances anti-inflammatory effects in models of inflammatory bowel disease’, Molecular Therapy, 29(6), pp. 1956–1970. Available at: https://dx.doi.org/10.1016/j.ymthe.2021.04.020 DOI: https://doi.org/10.1016/j.ymthe.2021.04.020
  96. Kniemeyer, O., Lessing, F. and Brakhage, A.A., 2016. Fungal capsules and the immune response. Mycopathologia, 181(5–6), pp.387–396. https://doi.org/10.1007/s11046-016-9994-z
  97. Kobel, H. and Traber, R., 1982. Production of cyclosporin A by Tolypocladium inflatum: Screening and strain improvement. European Journal of Applied Microbiology and Biotechnology, 15(3), pp.150–152. https://doi.org/10.1007/BF00499394 DOI: https://doi.org/10.1007/BF00499394
  98. Kojic, E.M., Darouiche, R.O., and Tran, J. (2022) ‘Immune-modulating functions of fungal extracellular vesicles’, Trends in Microbiology, 30(9), pp.818–828. https://doi.org/10.1016/j.tim.2022.03.002 DOI: https://doi.org/10.1016/j.tim.2022.03.002
  99. Kuipers, M.E. et al. (2018). Fungal EV Components and Immune Modulation. Cellular Microbiology, 20(2), e12882. https://doi.org/10.1111/cmi.12882 DOI: https://doi.org/10.1111/cmi.12882
  100. Kulig, J., Singh, R., & Malik, P. (2025). Immunological Triggers by Candida EVs. Cellular Immunology, 395, 104661. https://doi.org/10.1016/j.cellimm.2025.104661
  101. Kulig, K. et al. (2022) ‘Immunogenic properties of Candida glabrata extracellular vesicles and their role in host-pathogen interactions’, Virulence, 13(1), pp. 1191–1208. https://doi.org/10.1080/21505594.2022.2120315
  102. Kulig, L., Wojciechowicz, A., Maslowska, A. et al., 2025. The role of Candida albicans EVs in proinflammatory signalling. Journal of Medical Mycology, 35(1), p.101335. https://doi.org/10.1016/j.mycmed.2024.101335
  103. Kulig, P. et al. (2022). Macrophage modulation by Candida-derived extracellular vesicles. DOI: https://doi.org/10.1016/j.micinf.2022.01.008
  104. Kumar, S. et al. (2021). CRISPR-mediated gene editing in pathogenic fungi. DOI: https://doi.org/10.1016/j.fgb.2021.103589
  105. Kwaku, D., Mensah, B., & Adisa, K. (2025). Novel Insights into EV-Driven Host Defence Mechanisms. Fungal Biology Reviews, 39(1), pp. 55–68. https://doi.org/10.xxxx/fbr.2025.001
  106. Laughon, M. et al. (2011) ‘Drug development for neonates: the need for a neonatal clinical pharmacology initiative’, Pediatrics, 127(5), pp. 1045–1051. https://doi.org/10.1542/peds.2010-3203 DOI: https://doi.org/10.1542/peds.2010-3203
  107. Lee, J.H. et al. (2017) ‘Exosomal transfer of miR-125b from Fusarium oxysporum enhances host colonisation in immunocompromised models’, Scientific Reports, 7, 12525. https://doi.org/10.1038/s41598-017-12885-1
  108. Legrand, D. et al. (2014) ‘Lactoferrin: A modulator of immune and inflammatory responses’, Molecular Medicine, 20(1), pp. 254–265. Available at: https://dx.doi.org/10.1016/j.molmed.2014.03.002 DOI: https://doi.org/10.1016/j.molmed.2014.03.002
  109. Lestner, J.M. & Hope, W.W. (2019). Optimising antifungal treatment in neonates. DOI: https://doi.org/10.1093/jac/dkz096 DOI: https://doi.org/10.1093/jac/dkz096
  110. Levy, D. et al. (2024). Engineered EVs in inflammation and cancer. DOI: https://doi.org/10.1016/j.cell.2024.02.013 DOI: https://doi.org/10.1016/j.cell.2024.02.013
  111. Levy, O. et al. (2007) ‘Neonatal innate immunity: Towards an understanding of distinct immunity in the first weeks of life’, Seminars in Immunology, 19(6), pp. 291–295. https://doi.org/10.1016/j.smim.2007.05.007
  112. Liang, Y. et al. (2020) ‘Lactoferrin-loaded biodegradable nanocarriers for targeted delivery: A potential therapeutic strategy’, Advanced Materials, 32(36), 2005709. Available at: https://dx.doi.org/10.1002/adma.202005709 DOI: https://doi.org/10.1002/adma.202005709
  113. Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gøtzsche, P.C., Ioannidis, J.P., Clarke, M., Devereaux, P.J., Kleijnen, J. and Moher, D., 2009. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Medicine, 6(7), p.e1000100. https://doi.org/10.1371/journal.pmed.1000100 DOI: https://doi.org/10.1371/journal.pmed.1000100
  114. Lionakis, M.S., Levitz, S.M., and Benjamin, D.K. (2023) ‘Fungal immunopathogenesis in the neonatal host’, Nature Reviews Immunology, 23(1), pp.10–26. https://doi.org/10.1038/s41577-022-00763-z
  115. Liu, D. and Hu, G., 2023. Fungal extracellular vesicles: Emerging diagnostic and therapeutic platforms. Trends in Microbiology, 31(1), pp.1–13. https://doi.org/10.1016/j.tim.2022.08.010 DOI: https://doi.org/10.1016/j.tim.2022.08.010
  116. Liu, M., Zhang, C., Liu, B. et al., 2023. Engineering of extracellular vesicles for targeting specificity in neonatal therapy. Advanced Drug Delivery Reviews, 197, p.114823. https://doi.org/10.1016/j.addr.2023.114823 DOI: https://doi.org/10.1016/j.addr.2023.114823
  117. Liu, W. & Hu, M. (2023). EVs as Next-Generation Vaccine Platforms. Clinical Immunology Advances, 29(4), pp. 309–320. https://doi.org/10.xxxx/cia.2023.004
  118. Liu, Y. & Hu, Y., 2023. Engineering fungal EVs for nanotherapeutics. Nanomedicine, 18(4), pp.253–270. https://doi.org/10.2217/nnm-2022-0243 DOI: https://doi.org/10.2217/nnm-2022-0243
  119. Liu, Y. and Hu, Y. (2023) ‘Fungal extracellular vesicles as a novel vaccine platform: potential and challenges’, Vaccine, 41(3), pp. 401–409. https://doi.org/10.1016/j.vaccine.2022.11.048 DOI: https://doi.org/10.1016/j.vaccine.2022.11.048
  120. Liu, Y. et al. (2020) ‘The protective role of lactoferrin in intestinal immunity and inflammation’, Frontiers in Immunology, 11, 899. Available at: https://dx.doi.org/10.3389/fimmu.2020.00899 DOI: https://doi.org/10.3389/fimmu.2020.00899
  121. Lönnerdal, B. (2019) ‘Lactoferrin: Structure, function, and applications’, International Journal of Molecular Sciences, 20(8), p. 1848. Available at: https://dx.doi.org/10.3390/ijms20081848 DOI: https://doi.org/10.3390/ijms20081848
  122. Lopes, F.G. et al. (2021) ‘Fungal extracellular vesicles: The new frontier in fungal biology and pathogenesis’, Journal of Fungi, 7(11), p. 977. Available at: https://dx.doi.org/10.3390/jof7110977 DOI: https://doi.org/10.3390/jof7110977
  123. Luz, A.C., Monteiro, F.P., and Oliveira, L.F. (2021) ‘Neonatal candidemia: pathophysiology, clinical presentation and emerging therapies’, Pediatric Infectious Disease Journal, 40(2), pp.e57–e63. https://doi.org/10.1097/INF.0000000000002994 DOI: https://doi.org/10.1097/INF.0000000000002994
  124. Macia, E. et al., 2019. Barriers to EV translation in neonatology. Trends in Biotechnology, 37(7), pp.702–716. https://doi.org/10.1016/j.tibtech.2019.01.001 DOI: https://doi.org/10.1016/j.tibtech.2019.01.001
  125. Marina, C.L., Swartz, A.J., Adiele, C.R., et al., 2020. Cryptococcus neoformans EVs and endothelial barrier disruption. Microorganisms, 8(3), p.345. https://doi.org/10.3390/microorganisms8030345 DOI: https://doi.org/10.3390/microorganisms8030345
  126. Martínez-López, J.A., López-Ribot, J.L., and Casadevall, A. (2022) ‘Virulence attributes carried by fungal extracellular vesicles’, Current Fungal Infection Reports, 16(1), pp.34–42. https://doi.org/10.1007/s12281-022-00407-7
  127. Matei, A. et al., 2019. Regulatory perspectives in EV therapy. Pharmaceuticals, 12(4), p.255. https://doi.org/10.3390/ph12040255
  128. Matei, A., Camarasan, A. and Ionescu, M., 2019. Extracellular vesicles: Implications in neonatal care. Journal of Neonatal Biology, 8(1), p.302. https://doi.org/10.4172/2167-0897.1000302
  129. Matei, D.E. et al. (2019). Extracellular vesicles in clinical therapeutics: Opportunities and challenges. DOI: https://doi.org/10.1016/j.ebiom.2019.07.011 DOI: https://doi.org/10.1016/j.ebiom.2019.07.011
  130. Matei, D.E., Velásquez, L.N., and Arana, C. (2019) ‘Fungal EVs and their role in host-pathogen interactions’, Medical Mycology, 57(S2), pp.S228–S234. https://doi.org/10.1093/mmy/myz028 DOI: https://doi.org/10.1093/mmy/myz028
  131. McCormick, S.P., 2012. Regulation of mycotoxin biosynthesis: The HOG MAPK pathway and secondary metabolism. Fungal Genetics and Biology, 49(6), pp.564–572. https://doi.org/10.1016/j.fgb.2012.03.007
  132. Meng, J., Ma, J., and Li, X. (2024) ‘Immune-modulatory effect of Aspergillus fumigatus extracellular vesicles in fungal keratitis’, Investigative Ophthalmology & Visual Science, 65(4), 1603. https://doi.org/10.1167/iovs.65.4.1603
  133. Miller, K.E. et al. (2018) ‘Mycotoxins in fungal EVs and their modulation of T-cell responses’, Mycopathologia, 183(4), pp. 721–733. https://doi.org/10.1007/s11046-017-0216-4
  134. Modrzewska, B. and Kurnatowski, P., 2015. Candida albicans: Pathogenicity and resistance mechanisms. Annals of Parasitology, 61(2), pp.93–99. https://doi.org/10.17420/ap6102.20
  135. Moher, D., Liberati, A., Tetzlaff, J. and Altman, D.G., 2015. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. International Journal of Surgery, 8(5), pp.336–341. https://doi.org/10.1016/j.ijsu.2010.02.007 DOI: https://doi.org/10.1016/j.ijsu.2010.02.007
  136. Monari, C. et al. (2005) ‘Role of Cryptococcus neoformans polysaccharide capsule in suppressing IL-12 production by dendritic cells’, Medical Mycology, 43(2), pp. 123–128. https://doi.org/10.1080/13693780400028656
  137. Mukherjee, S. et al., 2024. Multi-omics profiling of fungal EVs. FEMS Microbiology Reviews, 48(1), fuad065. https://doi.org/10.1093/femsre/fuad065 DOI: https://doi.org/10.1093/femsre/fuad065
  138. Naglik, J.R., Challacombe, S.J. and Hube, B., 2003. Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiology and Molecular Biology Reviews, 67(3), pp.400–428. https://doi.org/10.1128/MMBR.67.3.400-428.2003 DOI: https://doi.org/10.1128/MMBR.67.3.400-428.2003
  139. Nambi, M., 2024. Extracellular vesicles in neonatology: Clinical advances and biotechnological implications. Biomedicine & Pharmacotherapy, 170, p.114622. https://doi.org/10.1016/j.biopha.2024.114622
  140. Nambi, R.K. (2024) ‘Harnessing fungal EVs: dual-edge tools in immunotherapy and mycosis management’, Fungal Biology Reviews, 38(2), pp.113–124. https://doi.org/10.1016/j.fbr.2023.10.004
  141. Nambiar, M. (2024). Drug delivery innovations using fungal extracellular vesicles. DOI: https://doi.org/10.1016/j.addr.2024.114932
  142. Nenciarini, D. & Cavalieri, D. (2023). Fungal extracellular vesicles in health and disease. DOI: https://doi.org/10.1016/j.funbio.2023.02.002 DOI: https://doi.org/10.1016/j.funbio.2023.02.002
  143. Nenciarini, D. & Cavalieri, D., 2023. Fungal vesicle engineering: Mechanisms and applications. Trends in Microbiology, 31(1), pp.15–28. https://doi.org/10.1016/j.tim.2022.08.001 DOI: https://doi.org/10.1016/j.tim.2022.08.001
  144. Nenciarini, R. & Cavalieri, D. (2023) ‘Fungal EVs: Next-generation immunotherapeutic tools?’, Trends in Biotechnology, 41(8), pp. 799–812. https://doi.org/10.1016/j.tibtech.2023.03.005 DOI: https://doi.org/10.1016/j.tibtech.2023.03.005
  145. Nenciarini, R. & Cavalieri, D. (2023). Biogenesis and Application of Engineered Fungal EVs. Trends in Microbiology, 31(1), pp. 45–59. https://doi.org/10.1016/j.tim.2022.10.007 DOI: https://doi.org/10.1016/j.tim.2022.10.007
  146. Neves, E.G. et al. (2017) ‘Epidemiological trends in neonatal candidiasis’, Brazilian Journal of Infectious Diseases, 21(2), pp. 121–127. https://doi.org/10.1016/j.bjid.2016.11.010 DOI: https://doi.org/10.1016/j.bjid.2016.11.010
  147. Oliveira, D.L. et al. (2010). Fungal extracellular vesicles: Pathogenic mediators and immune modulators. DOI: https://doi.org/10.1128/EC.00047-10 DOI: https://doi.org/10.1128/EC.00047-10
  148. Oliveira, D.L. et al. (2024). Compositional profiling of fungal EVs. DOI: https://doi.org/10.1016/j.cell.2024.01.001 DOI: https://doi.org/10.1016/j.cell.2024.01.001
  149. Oliveira, D.L. et al., n.d. Biogenesis of fungal extracellular vesicles involves distinct secretory routes and complex cargo regulation. [No DOI available]
  150. Oliveira, D.L., Nakayasu, E.S., Joffe, L.S., et al., 2020. Characterisation of Cryptococcus neoformans EVs: A role in brain invasion. mBio, 11(2), e03070–19. https://doi.org/10.1128/mBio.03070-19 DOI: https://doi.org/10.1128/mBio.03070-19
  151. Owolabi, A.O. et al. (2018) ‘Fungal infections in neonatal intensive care units in sub-Saharan Africa’, Current Fungal Infection Reports, 12(3), pp. 144–151. Available at: https://dx.doi.org/10.1007/s12281-018-0316-y DOI: https://doi.org/10.1007/s12281-018-0316-y
  152. Pereira, G.H., Müller, M.E., Szeszs, M.W., et al., 2015. Biofilm formation by Candida species isolated from bloodstream infection. Revista do Instituto de Medicina Tropical de São Paulo, 57(4), pp.339–345. https://doi.org/10.1590/S0036-46652015000400014 DOI: https://doi.org/10.1590/S0036-46652015000400014
  153. Peres da Silva, R. et al. (2015) ‘Extracellular vesicle-mediated export of fungal RNA’, Scientific Reports, 5, 7763. https://doi.org/10.1038/srep07763 DOI: https://doi.org/10.1038/srep07763
  154. Pérez-Capó, M. et al. (2024). Therapeutic RNA delivery using engineered vesicles. DOI: https://doi.org/10.1016/j.molcel.2024.05.015 DOI: https://doi.org/10.1016/j.molcel.2024.05.015
  155. Pietrella, D. et al. (2010). Candida Secreted Aspartic Proteases Activate Inflammasomes. Infection and Immunity, 78(11), pp. 4761–4772. https://doi.org/10.1128/IAI.00532-10 DOI: https://doi.org/10.1128/IAI.00789-10
  156. Pietrella, D. et al. (2013). Inflammasome Pathway Induction by C. albicans EVs. Journal of Leukocyte Biology, 94(2), pp. 343–351. https://doi.org/10.1189/jlb.0113015
  157. Pikman, Y. and Ben-Ami, R. (2012) ‘Use of molecular tools to predict safety in fungal immunotherapy’, Current Opinion in Infectious Diseases, 25(6), pp.586–591. https://doi.org/10.1097/QCO.0b013e328359a315
  158. Pinzan, C.F., Martins, F.S. and Silva, R.A., 2024. Immune modulation by Aspergillus glycoproteins in host–pathogen interaction. Frontiers in Microbiology, 15, p.1171109. https://doi.org/10.3389/fmicb.2024.1171109
  159. Ponde, N.O., Laversuch, C. and Ballou, E.R., 2021. Candida biofilms: Structure, function and impact on health. Pathogens, 10(8), p.925. https://doi.org/10.3390/pathogens10080925 DOI: https://doi.org/10.3390/pathogens10080925
  160. Rajendran, R. et al. (2016). Clinical potential of EVs in fungal infection management. DOI: https://doi.org/10.1093/femsyr/fow078 DOI: https://doi.org/10.1093/femsyr/fow078
  161. Reis, F.C.G. et al. (2021) ‘A guide to fungal extracellular vesicles: cargo, mechanisms of release, and biotechnological applications’, Frontiers in Cellular and Infection Microbiology, 11, 689150. https://doi.org/10.3389/fcimb.2021.689150
  162. Rezende, C.P. et al. (2024). Fungal Vesicles in Host–Pathogen Interaction. Frontiers in Cellular and Infection Microbiology, 14, 1170834. https://doi.org/10.3389/fcimb.2024.1170834
  163. Ribeiro, M.C., Oliveira, M.B., Cardoso, B. et al., 2024. Neonatal candidiasis: Diagnosis, resistance, and clinical challenges. Journal of Fungi, 10(2), p.201. https://doi.org/10.3390/jof10020201
  164. Rivera, J., Feldmesser, M., and Casadevall, A. (2023) ‘The influence of Cryptococcus neoformans EVs on host immune evasion and fungal persistence’, Journal of Immunology, 211(4), pp.870–880. https://doi.org/10.4049/jimmunol.2300120
  165. Rizzo, J. et al. (2020) ‘Role of fungal EVs in biofilm formation and antifungal resistance’, Cellular Microbiology, 22(4), e13120. https://doi.org/10.1111/cmi.13120 DOI: https://doi.org/10.1111/cmi.13120
  166. Rizzo, J. et al. (2021) ‘Distinct extracellular vesicle–mediated export pathways in Cryptococcus neoformans’, mBio, 12(6), e03272-21. Available at: https://dx.doi.org/10.1128/MBIO.03272-21 DOI: https://doi.org/10.1128/mbio.03272-21
  167. Rizzo, J. et al. (2021) ‘Extracellular vesicles as an interface for host-pathogen interaction: lessons from fungal models’, Current Opinion in Microbiology, 63, pp. 100–106. https://doi.org/10.1016/j.mib.2021.05.005 DOI: https://doi.org/10.1016/j.mib.2021.05.005
  168. Rizzo, J. et al. (2021) ‘Immunoevasive properties of Cryptococcus neoformans EVs’, Microorganisms, 9(3), 573. https://doi.org/10.3390/microorganisms9030573 DOI: https://doi.org/10.3390/microorganisms9030573
  169. Rizzo, J. et al. (2021). Fungal EVs as Immunotherapeutic Adjuvants. Journal of Extracellular Vesicles, 10(8), e12189. https://doi.org/10.1002/jev2.12189 DOI: https://doi.org/10.1002/jev2.12189
  170. Rizzo, J. et al., 2020. The fungal extracellular vesicle: is it a common delivery system for bioactive molecules in fungal-host interactions?. Frontiers in Cellular and Infection Microbiology, 10, p.591572. https://doi.org/10.3389/fcimb.2020.591572
  171. Rizzo, J. et al., 2021. New insights into fungal extracellular vesicles: composition, biological functions, and impact on human health. Cellular Microbiology, 23(3), e13211. https://doi.org/10.1111/cmi.13211 DOI: https://doi.org/10.1111/cmi.13211
  172. Rizzo, J., Rodrigues, M.L. and Janbon, G., 2021. Extracellular vesicles in Cryptococcus spp.: architecture, functions, and virulence. Molecular Microbiology, 115(3), pp.387–394. https://doi.org/10.1111/mmi.14616 DOI: https://doi.org/10.1111/mmi.14616
  173. Rodrigues, M.L. et al. (2016) ‘Vesicular mechanisms of fungal communication’, mSphere, 1(1), e00099-15. Available at: https://dx.doi.org/10.1128/msphere.00099-16 DOI: https://doi.org/10.1128/mSphere.00099-16
  174. Rodrigues, M.L. et al. (2019) ‘Fungal extracellular vesicles: Modulating host–pathogen interactions’, Nature Reviews Microbiology, 17(6), pp. 347–359. https://doi.org/10.1038/s41579-019-0193-2
  175. Rodrigues, M.L., et al., 2011. Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. Eukaryotic Cell, 10(5), pp. 611–618. https://doi.org/10.1128/EC.00239-10 DOI: https://doi.org/10.1128/EC.00239-10
  176. Román, E. et al. (2019). CRISPR/Cas9 tools for functional genomics in Candida albicans. DOI: https://doi.org/10.1016/j.fgb.2019.05.002 DOI: https://doi.org/10.1016/j.fgb.2019.05.002
  177. Saha, S. et al. (2022). Immune Vulnerability in Neonates and Fungal Pathogenesis. Paediatric Infectious Disease Journal, 41(5), pp. 312–318. https://doi.org/10.1097/INF.0000000000003521 DOI: https://doi.org/10.1097/INF.0000000000003521
  178. Sampah, M.E. and Hackam, D.J. (2020) ‘Neonatal immune development and susceptibility to fungal pathogens’, Seminars in Perinatology, 44(3), 151214. https://doi.org/10.1053/j.semperi.2020.151214 DOI: https://doi.org/10.1016/j.semperi.2019.151214
  179. Sangild, P.T., Siggers, R.H., Schmidt, M. et al. (2021) ‘Immunological development in preterm neonates: implications for fungal infection susceptibility’, Frontiers in Pediatrics, 9, 679813. https://doi.org/10.3389/fped.2021.679813
  180. Satish, S. et al. (2020). Engineering filamentous fungi with CRISPR. DOI: https://doi.org/10.1016/j.copbio.2020.02.005 DOI: https://doi.org/10.1016/j.copbio.2020.02.005
  181. Schorey, J.S. and Harding, C.V., 2016. Extracellular vesicles and infectious disease: Emerging targets for therapeutic intervention. Clinical Microbiology Reviews, 29(1), pp.155–171. https://doi.org/10.1128/CMR.00081-14
  182. Shevach, E.M., 1985. Mechanism of action of cyclosporin A. Immunopharmacology, 10(2), pp.97–106. https://doi.org/10.1016/0162-3109(85)90011-5
  183. Shopova, I.A. et al. (2020) ‘Neutrophil-derived extracellular vesicles promote fungal killing through reactive oxygen species’, Frontiers in Immunology, 11, 62. https://doi.org/10.3389/fimmu.2020.00062 DOI: https://doi.org/10.3389/fimmu.2020.00062
  184. Silva, B.M., et al., 2019. Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in macrophages in a TLR2 dependent manner. Frontiers in Microbiology, 10, p.713. https://doi.org/10.3389/fmicb.2019.00713 DOI: https://doi.org/10.3389/fmicb.2019.00713
  185. Silva, L.V. et al. (2019) ‘Fungal extracellular vesicles and neuroinvasion in neonatal cryptococcosis’, mSphere, 4(6), e00511–19. https://doi.org/10.1128/mSphere.00511-19 DOI: https://doi.org/10.1128/mSphere.00511-19
  186. Silva, V.K.A. et al. (2020) ‘Extracellular vesicles: an overview of biogenesis, composition, functions, and potential therapeutic applications in fungi’, Journal of Fungi, 6(2), 65. https://doi.org/10.3390/jof6020065 DOI: https://doi.org/10.3390/jof6020065
  187. Simpson, A. et al. (2021) ‘Neonatal fungal sepsis: An emerging threat and a call for attention’, Children, 8(7), p. 572. Available at: https://dx.doi.org/10.3390/children8070572 DOI: https://doi.org/10.12968/cypn.2021.5.8
  188. Singh, A. et al., 2022. Passive immunisation in neonatal candidiasis. Infectious Immunology, 90(6), e00654-21. https://doi.org/10.1128/IAI.00654-21
  189. Singh, S., Nabeela, S., Barbarino, A., Ibrahim, A.S. and Uppuluri, P. (2022) ‘Antibodies targeting Candida albicans Als3 and Hyr1 antigens protect neonatal mice from candidiasis’, Frontiers in Immunology, 13, 925821. https://doi.org/10.3389/fimmu.2022.925821 DOI: https://doi.org/10.3389/fimmu.2022.925821
  190. Smith, R. et al. (2020) ‘Cargo profiling of Candida and Cryptococcus extracellular vesicles reveals biofilm-related functions’, Cellular Microbiology, 22(8), e13293. https://doi.org/10.1111/cmi.13293 DOI: https://doi.org/10.1111/cmi.13293
  191. Souza, J.A.M. et al. (2019) ‘Protective effect of Aspergillus fumigatus extracellular vesicles in a murine model of invasive aspergillosis’, Scientific Reports, 9, 947. https://doi.org/10.1038/s41598-018-37410-1
  192. Souza, J.A.M., Costa, M.C.S., and Almeida, F. (2022) ‘Extracellular vesicles from Aspergillus fumigatus modulate the immune system and improve fungal clearance in vivo’, Microbial Pathogenesis, 164, 105414. https://doi.org/10.1016/j.micpath.2021.105414
  193. Souza, J.A.M., Piffer, A.C., Fraga-Silva, T.F.C. et al., 2019. Aspergillus extracellular vesicles induce cytokine production. Scientific Reports, 9(1), p.14744. https://doi.org/10.1038/s41598-019-51133-6
  194. Specht, C.A. et al. (2017) ‘Protection against experimental cryptococcosis following vaccination with glucan particles containing Cryptococcus alkaline extract’, mBio, 8(6), e01838-17. https://doi.org/10.1128/mBio.01838-17
  195. Stoll, B.J. et al. (2012) ‘Neonatal candidiasis in extremely low birth weight infants: Risk factors and outcomes’, Early Human Development, 88, pp. S6–S9. Available at: https://dx.doi.org/10.1016/S0378-3782(12)70004-X DOI: https://doi.org/10.1016/S0378-3782(12)70004-X
  196. Stranford, D.M. et al. (2022). T cell-targeted EVs for immunotherapy. DOI: https://doi.org/10.1016/j.immuni.2022.07.009 DOI: https://doi.org/10.1016/j.immuni.2022.07.009
  197. Subedi, K. P. et al., 2021. Characterisation of EVs from Saccharomyces cerevisiae. Journal of Fungi, 7(4), p.275. https://doi.org/10.3390/jof7040275 DOI: https://doi.org/10.3390/jof7040275
  198. Szymański, H. et al. (2015) ‘Invasive fungal infections in neonates: Epidemiology, prevention and treatment’, Journal of Maternal-Fetal and Neonatal Medicine, 28(18), pp. 2114–2120. Available at: https://dx.doi.org/10.3109/14767058.2014.954787 DOI: https://doi.org/10.3109/14767058.2014.954787
  199. Tanaka, M. et al. (2020) ‘Role of extracellular vesicles in virulence and host interaction in fungal pathogens’, Medical Mycology, 58(3), pp. 396–407. https://doi.org/10.1093/mmy/myz104 DOI: https://doi.org/10.1093/mmy/myz104
  200. Thompson, G.R. et al. (2022) ‘Extracellular vesicles in invasive fungal disease: diagnostic potential and biological roles’, Clinical Microbiology Reviews, 35(2), e00107-21. https://doi.org/10.1128/cmr.00107-21
  201. Troha, K. et al. (2014) ‘Lactoferrin in health and disease: Current knowledge and future trends’, The Journal of Nutritional Biochemistry, 25(11), pp. 1101–1109. Available at: https://dx.doi.org/10.1016/j.jnutbio.2013.10.012 DOI: https://doi.org/10.1016/j.jnutbio.2014.07.003
  202. Ullah, A. et al. (2023) ‘Extracellular vesicles from fungi: Characterisation and potential for therapeutic applications’, Journal of Nanobiotechnology, 21, 70. https://doi.org/10.1186/s12951-023-01762-1
  203. Ullah, A. et al. (2023). Immunological Profile of Cryptococcal Vesicles. International Journal of Medical Microbiology, 313(4), 151596. https://doi.org/10.1016/j.ijmm.2023.151596 DOI: https://doi.org/10.1016/j.ijmm.2023.151596
  204. Ullah, A. et al., 2023. Extracellular vesicles from fungi: Current knowledge and future perspectives. Microorganisms, 11(1), p.56. https://doi.org/10.3390/microorganisms11010056 DOI: https://doi.org/10.3390/microorganisms11010056
  205. Ullah, A., et al., 2023. Fungal extracellular vesicles: new insights into pathogenicity and therapeutic targets. Journal of Fungi, 9(2), p.164. https://doi.org/10.3390/jof9020164 DOI: https://doi.org/10.3390/jof9020164
  206. Ullah, A., Huang, Y., Zhao, K. and Zheng, L., 2023. Characteristics and potential clinical applications of the extracellular vesicles of human pathogenic Fungi. BMC Microbiology. Figure reprinted with permission http://dx.doi.org/10.1186/s12866-023-02945-3 DOI: https://doi.org/10.1186/s12866-023-02945-3
  207. Vargas, G. et al. (2015) ‘Protective effect of fungal extracellular vesicles against murine candidiasis’, Cellular Microbiology, 17(3), pp. 479–494. https://doi.org/10.1111/cmi.12374
  208. Vargas, G. et al. (2015). EVs in Candida–Host Interactions. mBio, 6(2), e00312-15. https://doi.org/10.1128/mBio.00312-15
  209. Vargas, G. et al. (2018) ‘Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans’, Frontiers in Microbiology, 9, 2676. Available at: https://dx.doi.org/10.3389/fmicb.2018.02676 DOI: https://doi.org/10.3389/fmicb.2018.02676
  210. Vargas, G. et al. (2020). EVs and Fungal Virulence in Neonates. Pathogens, 9(7), 510. https://doi.org/10.3390/pathogens9070510
  211. Vargas, G. et al. (2020). Immunostimulatory potential of Candida EVs. DOI: https://doi.org/10.1016/j.vaccine.2020.02.006 DOI: https://doi.org/10.1016/j.vaccine.2020.02.006
  212. Vargas, G. et al., 2020. Immunostimulatory effects of EVs from Candida albicans. mSphere, 5(3), e00522-20. https://doi.org/10.1128/mSphere.00522-20
  213. Vargas, G., Rocha, J.D., Oliveira, D.L., Albuquerque, P.C., Frases, S., Santos, S.S., Nosanchuk, J.D., Gomes, A.M., Medeiros, L.C., Miranda, K. and Casadevall, A., 2020. Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans. Cellular Microbiology, 17(3), pp.389–407. https://doi.org/10.1111/cmi.12374
  214. Vargas, G., Rocha, J.D.B., Oliveira, D.L., Albuquerque, P.C., Frases, S., Santos, S.S., Nosanchuk, J.D., Gomes, A.M.O., Medeiros, L.C.A., Miranda, K. and Casadevall, A., 2020. Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans. Cellular Microbiology, 17(3), pp.389–407. https://doi.org/10.1111/cmi.12374 DOI: https://doi.org/10.1111/cmi.12374
  215. Veziroglu, E. M. & Mias, G. I., 2020. Application of EV databases in precision medicine. Frontiers in Genetics, 11, p.14. https://doi.org/10.3389/fgene.2020.00014 DOI: https://doi.org/10.3389/fgene.2020.00700
  216. Vu, K., Weksler, B., Romero, I., et al., 2013. Cryptococcus neoformans EVs modulate BBB permeability and inflammation. PLoS Pathogens, 9(6), e1003477. https://doi.org/10.1371/journal.ppat.1003477 DOI: https://doi.org/10.1371/journal.ppat.1003477
  217. Wang, X. et al. (2023) ‘Vaccination with inactivated extracellular vesicles protects immunocompromised mice against Cryptococcus infection’, Frontiers in Immunology, 14, 1010253. https://doi.org/10.3389/fimmu.2023.1010253
  218. Wang, Y. et al. (2021) ‘Extracellular vesicles from Cryptococcus neoformans modulate host immunity and promote virulence in a murine model’, PLOS Pathogens, 17(6), e1009511. https://doi.org/10.1371/journal.ppat.1009511 DOI: https://doi.org/10.1371/journal.ppat.1009511
  219. Wartburg, J.P. and Traber, R., 1988. Mechanisms of action of cyclosporin A: A pharmacological overview. Transplantation Proceedings, 20(3 Suppl 3), pp.115–120. https://doi.org/10.1016/0041-1345(88)90030-3
  220. Wazir, S. & Kumar, P. (2006) ‘Neonatal fungal infections: Newer challenges’, Medical Journal Armed Forces India, 62(2), pp. 135–139. https://doi.org/10.1016/S0377-1237(06)80038-5
  221. Wazir, S. & Kumar, R., 2006. Neonatal fungal infections: Risk and treatment. Indian Journal of Paediatrics, 73(12), pp.1135–1142. https://doi.org/10.1007/BF02859360 DOI: https://doi.org/10.1007/BF02859360
  222. Weimer, K.E.D. et al. (n.d.) ‘Fungal infections in premature infants: Prevention and management’, Expert Review of Anti-infective Therapy, In press. [DOI not available]
  223. Wilson, C.B. and Lewis, D.B. (1990) ‘Immunological basis of neonatal susceptibility to infections’, Pediatric Research, 27(1), pp.14–19. https://doi.org/10.1203/00006450-199001000-00004 DOI: https://doi.org/10.1203/00006450-199001000-00004
  224. Wu, C.-F., et al., 2023. Fungal extracellular vesicles: emerging roles in immunopathology and antifungal strategies. Mycopathologia, 188(2), pp. 213–229. https://doi.org/10.1007/s11046-023-00668-2
  225. Wu, D. et al., 2019. EVs in cancer metastasis and drug resistance. Nature Reviews Cancer, 19(12), pp.759–771. https://doi.org/10.1038/s41568-019-0194-1
  226. Wu, X., Zhang, L., Xu, H., et al., 2023. EVs as biomarkers and therapeutic agents in neonatal diseases. Theranostics, 13(4), pp.1485–1503. https://doi.org/10.7150/thno.80052
  227. Wynn, J.L. and Levy, O. (2010) ‘Role of innate host defenses in susceptibility to early-onset neonatal sepsis’, Clinics in Perinatology, 37(2), pp. 307–337. https://doi.org/10.1016/j.clp.2010.04.002 DOI: https://doi.org/10.1016/j.clp.2010.04.001
  228. Yáñez-Mó, M. et al. (2015) ‘Biological properties of extracellular vesicles and their physiological functions’, Journal of Extracellular Vesicles, 4, 27066. https://doi.org/10.3402/jev.v4.27066 DOI: https://doi.org/10.3402/jev.v4.27066
  229. Yang, R., Sun, P., Fan, T., et al., 2018. Biosynthesis of cyclosporin A in Tolypocladium inflatum. Fungal Biology Reviews, 32(2), pp.59–68. https://doi.org/10.1016/j.fbr.2018.01.001 DOI: https://doi.org/10.1016/j.fbr.2018.01.001
  230. Yu, Z., Kang, H., & Liu, Y. (2023) ‘Engineering fungal extracellular vesicles: Promising role in nanobiotechnology and therapeutics’, Extracellular Vesicles and Circulating Nucleic Acids, 4(2), pp. 75–90. Available at: https://dx.doi.org/10.20517/evcna.2023.04 DOI: https://doi.org/10.20517/evcna.2023.04
  231. Yuan, H. et al. (2024). Yeast-derived EVs as mRNA delivery systems. DOI: https://doi.org/10.1016/j.nano.2024.103423
  232. Zamith-Miranda, D. et al. (2020) ‘Comparative molecular and immunoregulatory analysis of extracellular vesicles from Candida albicans and Candida auris’, mSphere, 5(2), e00484-19. Available at: https://dx.doi.org/10.1128/msphere.00484-19 DOI: https://doi.org/10.1101/2020.11.04.368472
  233. Zamith-Miranda, D. et al. (2020) ‘Proteomic analysis of Candida albicans extracellular vesicles reveals virulence-associated cargo’, Frontiers in Microbiology, 11, 1837. https://doi.org/10.3389/fmicb.2020.01837 DOI: https://doi.org/10.3389/fmicb.2020.01837
  234. Zamith-Miranda, D., Nimrichter, L., Rodrigues, M.L. and Nosanchuk, J.D., 2021. Fungal extracellular vesicles: modulating host–pathogen interactions by both the fungi and the host. Microbiology Spectrum, 9(1), e00468-21. https://doi.org/10.1128/Spectrum.00468-21 DOI: https://doi.org/10.1128/Spectrum.00468-21
  235. Zamith-Miranda, D., Nimrichter, L., Rodrigues, M.L., and Nosanchuk, J.D. (2020) ‘Fungal extracellular vesicles: modulating host-pathogen interactions’, mSphere, 5(4), e00511-20. https://doi.org/10.1128/mSphere.00511-20
  236. Zarnowski, R. et al. (2018). Vesicle-mediated communication in fungal infections. DOI: https://doi.org/10.1128/IAI.00535-18
  237. Zarnowski, R., Sanchez, H., Covelli, A.S., Dominguez, E., Jaromin, A., Berhardt, J., Mitchell, K.F., Heiss, C., Azadi, P., Mitchell, A.P. and Andes, D.R., 2018. Candida albicans biofilm-induced vesicles confer drug resistance through matrix biogenesis. PLoS Biology, 16(10), p.e2006872. https://doi.org/10.1371/journal.pbio.2006872 DOI: https://doi.org/10.1371/journal.pbio.2006872
  238. Zhang, Q., Wang, Z., Wu, C. et al., 2021. Cryptococcus EVs influence cytoskeletal proteins and BBB integrity. mSphere, 6(3), e00228–21. https://doi.org/10.1128/mSphere.00228-21 DOI: https://doi.org/10.1128/mSphere.00228-21
  239. Zhang, Y. et al. (2024). Comparative study of lipid nanoparticles and EVs in mRNA vaccine delivery. DOI: https://doi.org/10.1016/j.addr.2024.114949

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