Fungal Extracellular Vesicles: New Perspectives in Intercellular Communication, Pathogenicity, and Host-Pathogen Interactions
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Abstract
Fungal Extracellular Vesicles (FEVs) are now recognized as crucial vectors of intercellular communication within fungal ecosystems and during host interactions. They transport proteins, lipids, and nucleic acids—modulating virulence, facilitating tissue invasion, and promoting immune evasion. This review consolidates recent findings on the definition, classification, and communication processes of FEVs and their pathogenic and immunomodulatory roles. Methods for vesicle characterization, potential therapeutic applications, and the challenges arising from their variability are also discussed. All this knowledge paves the way for interdisciplinary approaches to better understand and combat fungal infections.
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Albuquerque PC, Nakayasu ES, Rodrigues ML. Fungal extracellular vesicles as modulators of host immunity. Nat Microbiol. 2018;3(12):1354–1361.
Bleackley MR, Dawson CS, Anderson MA. Fungal extracellular vesicles with a focus on proteomic analysis. J Extracell Vesicles. 2019;8(1):1565277. Available from: https://doi.org/10.1002/pmic.201800232
Jenks JD, Hoenigl M. The antifungal pipeline: Update on current and emerging therapeutics for fungal infections. Curr Fungal Infect Rep. 2023;17(3):151–162.
Rodrigues ML, Nosanchuk JD. Fungal extracellular vesicles: Biological roles and potential applications. J Fungi (Basel). 2021;7(7):553. Available from: https://link.springer.com/book/10.1007/978-3-030-83391-6
Bielska E, Sisquella MA, Aldeieg M, Birch C, O’Donoghue EJ, May RC. The role and therapeutic potential of fungal extracellular vesicles. Nat Rev Microbiol. 2022;20(11):669–683.
Rodrigues ML, Casadevall A. The fifth kingdom and its extracellular vesicles. PLoS Pathog. 2022;18(6):e1010539.
Van Niel G, Dunsford LNR, Lázaro-Ibáñez E, et al. The multifaceted roles of extracellular vesicle subpopulations in health and disease. Nat Rev Mol Cell Biol. 2023;24(10):717–736.
Rodrigues ML, Nimrichter L, Oliveira DL, Nosanchuk JD, Casadevall A. Vesicular transport in fungi: A comparison with eukaryotic and prokaryotic cells. Annu Rev Microbiol. 2021;75:351–370.
Higuchi A, Morishita M, Nagata R, Maruoka K, Katsumi H, Yamamoto A. Functional characterization of extracellular vesicles from Baker’s yeast Saccharomyces cerevisiae as a novel vaccine material for immune cell maturation. J Pharm Sci. 2023;112(1):525–534. Available from: https://doi.org/10.1016/j.xphs.2022.08.032
Lopez J, Tait SWG. Mitochondrial control of apoptosis: The apoptosome and beyond. Nat Rev Mol Cell Biol. 2023;24(10):732–749.
Semighini CP, Harrison TS. Programmed cell death in fungi: The knowns and unknowns. J Fungi (Basel). 2021;7(9):746.
Reginato JZ, Gandra RM, Kischkel B. Exposure to caspofungin changes the protein content of extracellular vesicles produced by Candida albicans and their interaction with macrophages. J Fungi (Basel). 2023;9(2):263.
Rella A, Farnoud AM, Del Poeta M. Extracellular vesicles in fungal stress response and adaptation. J Fungi (Basel). 2023;9(6):617.
Brown L, Wolf JM, Prados-Rosales R, Casadevall A. Through the wall: Extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol. 2015;13(10):620–630. Available from: https://doi.org/10.1038/nrmicro3480
Xie J, Haesebrouck F, Van Hoecke L, Vandenbroucke RE. Bacterial extracellular vesicles: An emerging avenue to tackle diseases. Trends Microbiol. 2023 Dec;31(12):1206–1224. Available from: https://doi.org/10.1016/j.tim.2023.05.010
Wang J, Li W, Lu R. Fungal extracellular vesicles: A review of their biogenesis, cargoes, and functions. Front Microbiol. 2022;13:862413.
Yin Z, Smith AG, Brown GD. Tumor-derived exosomes mimic pathogen signaling mechanisms. Trends Immunol. 2022;43(5):321–335.
Rizzo J, Rodrigues ML, Janbon G. Fungal extracellular vesicles as key players in host-microbe interactions: From pathogenesis to biotechnology. PLoS Pathog. 2023;19(8):e1011603.
Martínez-López R, Hernáez ML, Redondo E, Calvo G, Radau S, Pardo M, et al. Candida albicans hyphal extracellular vesicles are different from yeast ones, carrying an active proteasome complex and showing a different role in host immune response. Microbiol Spectr. 2022 Jun 29;10(3):e0069822. Available from: https://doi.org/10.1128/spectrum.00698-22
Zaragoza O, Rodrigues ML, De Oliveira HC. Extracellular vesicles in Cryptococcus neoformans: Insights into polysaccharide export and virulence. J Fungi (Basel). 2023;9(3):301.
Hai TP, Nga TTT, Van Anh DT. The roles of extracellular vesicles in fungal pathogenesis and antifungal drug resistance. J Fungi (Basel). 2023;9(11):1055.
Souza AC, Pina A, Pinto MR, et al. Aspergillus fumigatus extracellular vesicles modulate human neutrophil response. mSphere. 2022;7(4):e0019922.
Jiang L, Huang Y, Chen Q. Fungal small RNAs suppress plant immunity by hijacking host RNA interference pathways. Science. 2023;379(6638):eabo1934.
He B, Liu T, Jin H. Extracellular RNAs and vesicles in cross-kingdom RNAi. Curr Opin Plant Biol. 2021;61:102020.
Zanini D, Wawra S. Fungal small RNAs and their roles in plant-pathogen interactions. Int J Mol Sci. 2023;24(18):14207.
Zarnowski R, Noll A, Andes DR. The role of extracellular vesicles in inter-kingdom communication of fungi. Curr Opin Microbiol. 2022;69:102188.
De Oliveira HC, Nakayasu ES, Zaragoza O. Intracellular and extracellular roles of extracellular vesicles produced by Cryptococcus neoformans. J Fungi (Basel). 2021;7(4):290.
Herkert M, Kniemeyer O, Brakhage AA. Extracellular vesicles of fungi: Release, composition, and functions. FEMS Microbiol Rev. 2021;45(5):fuab028.
Liu Y, Wang J, Chen X, et al. Bacillus subtilis extracellular vesicles target Candida albicans biofilms via enzymatic degradation of extracellular matrix components. Nat Commun. 2024;15(1):1234.
Peres da Silva R, Longo LGV, Cunha JPCD, Sobreira TJP, Rodrigues ML, Faoro H, et al. Comparison of the RNA content of extracellular vesicles derived from Paracoccidioides brasiliensis and Paracoccidioides lutzii. Cells. 2019 Jul 23;8(7):765. Available from: https://doi.org/10.3390/cells8070765
Zarnowski R, Sanchez H, Covelli AS, Dominguez E, Jaromin A, Bernhardt J, et al. Candida albicans biofilm-induced vesicles confer drug resistance through matrix modification. mBio. 2018;9(5):e00972-18.
Dixon CL, Wu A, Fairn GD. Multifaceted roles and regulation of nucleotide-binding oligomerization domain-containing proteins. Front Immunol. 2023;14:1242659. Available from: https://doi.org/10.3389/fimmu.2023.1242659
Gonçalves SM, Lagrou K. Immune defences against fungal invaders—The role of pattern recognition receptors in the activation of innate antifungal immunity. J Fungi (Basel). 2021;7(6):478.
Oliveira DL, Nimrichter L, Rodrigues ML. Cryptococcus neoformans extracellular vesicles: Key players in fungal pathogenesis and host immune modulation. PLoS Pathog. 2023;19(9):e1011673.
Casadevall A, Coelho C, Alanio A. Mechanisms of Cryptococcus neoformans-mediated host damage. Front Immunol. 2018 Apr 30;9:855. Available from: https://doi.org/10.3389/fimmu.2018.00855
Kumar A, Kumar P, Prasad R. Extracellular vesicles of Candida albicans: A new paradigm in fungal pathogenesis. Crit Rev Microbiol. 2021;47(5):616–630.
Vallejo MC, Matsuo AL, Ganiko L. Extracellular vesicles from Paracoccidioides brasiliensis can induce the expression of fungal virulence traits in vitro and enhance infection in mice. Front Cell Infect Microbiol. 2021;11:635340.
Jung EH, Lee JS. Roles of extracellular vesicles in fungal pathogenesis and antifungal immunity. Int J Mol Sci. 2022;23(15):8454.
Turner L, Ciofu O, Häussler S. Pseudomonas aeruginosa extracellular vesicles deliver virulence factors and promote infection in human airway epithelial cells. Cell Microbiol. 2021;23(8):e13367.
Wang S, Peng R, Chen Y. Structural basis for GSDMD targeting by the Shigella E3 ligase IpaH7.8. Nat Commun. 2024;15(1):89.
Athman JJ, Wang Y, McDonald DJ. Bacterial outer membrane vesicles: A new paradigm in host-pathogen interactions. Microb Cell. 2021;8(1):1–16.
Bitto NJ, Chapman R, Pidot S. Acinetobacter baumannii outer membrane vesicles elicit tissue factor expression, promoting a procoagulant state. Cell Microbiol. 2023;25(3):e13550.
Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. Available from: https://doi.org/10.1080/20013078.2018.1535750
Cai Q, He B, Wang S. Plants secrete extracellular vesicles that are transported to fungal cells to inhibit their growth. Plant Cell. 2021;33(7):2156–2174.
Martínez-García R, López-Blanco JR, Pérez-Lago L. Gut-derived EVs mediate immune tolerance during helminth infection. Nat Commun. 2024;15(1):1234.
Honorato L, Gandra RM, ZLPS E, Silva LFD, Pessoni RA. Extracellular Vesicles of Candida albicans: Current Knowledge and Perspectives. J Fungi (Basel). 2022;8(8):825.
Zhao X, He G, Chen L, Li L. The role of extracellular vesicles from Candida albicans in inter-kingdom communication. Front Cell Infect Microbiol. 2021;11:746815.
Kobiela S, Priebe F, Gorniak M, Piłsyk S, Szymański P. Extracellular Vesicles of Candida albicans—Their Role in Pathogenesis and Interaction with the Host. Int J Mol Sci. 2022;23(24):15668.
Dawson CS, Garcia-Ceron D, Rajapaksha H, Faou P, Anderson MA, Bleackley MR. Protein markers for fungal extracellular vesicles. Proteomics. 2020;20(21-22):e1900291.
Silva LP, Garcia AM, Ferreira SS, Oliveira MJ, Costa R, Pereira T. Role of Sur7 in the Biogenesis and Cargo Sorting of Candida albicans Extracellular Vesicles. J Fungi (Basel). 2024;10(3):456–475.
Brandt AC, Hasan MM, Alam MM, Lindsey RL, Colquhoun JM, Del Poeta M. The role of extracellular vesicles in fungal pathogenesis. PLoS Pathog. 2023;19(1):e1011044.
Tsavou A, Lysenkova LN, Karavyanskii DL. Candida albicans extracellular vesicles: Current state of knowledge and future perspectives. J Fungi (Basel). 2023;9(4):475.
Jachymek M, Lasek R, Ulańczyk Z, Brzezińska-Błaszczyk E, Słomińska-Wojewódzka M. Extracellular Vesicles from Candida albicans: New Players in Host-Pathogen Interactions. Int J Mol Sci. 2023;24(9):8223.
Brandt AC, Jones BK, Smith CD, Del Poeta M. Comparative analysis of extracellular vesicle composition in pathogenic Candida and Cryptococcus species. Fungal Genet Biol. 2024;178:103456.
Gandhi K, Kumar S, Sharma S, Khuller GK. Aspergillus flavus extracellular vesicles modulate macrophage functions and induce protective immunity. Med Mycol. 2022;60(1):myab077.
Gandhi K, Sharma S, Kumar S, Khuller GK. Proteomic profiling of extracellular vesicles from Aspergillus flavus reveals potential biomarkers for fungal endophthalmitis. J Proteomics. 2022;262:104600.
Zamith-Miranda D, Heyman HM, Cleare LG. Multi-omics approach unravels the impact of Candida auris extracellular vesicles on the virulence of this emerging fungal pathogen. mSphere. 2021;6(5):e00535-21.
Chan TS, Chen CH, Chen CH, Lee HH, Lee CH. Candida auris extracellular vesicles enhance adhesion to epithelial cells and modulate host immune responses. Front Cell Infect Microbiol. 2022;12:867263.
Rizzo J, Albuquerque PC, Wolf JM. Characterization of extracellular vesicles from the fungal pathogen Cryptococcus neoformans reveals features common to pathogenic fungi. mSphere. 2021;6(1):e01122-20.
Heo S, Kim HR, Kim MS. Cryptococcus neoformans UGG1, an endoplasmic reticulum quality control component, affects extracellular vesicle production and cargo, altering virulence. mBio. 2024;15(1):e0272423.
Reis FCG, Borges BS, Jozefowicz LJ. A novel peptide secreted in extracellular vesicles by Cryptococcus gattii induces melanization and confers protection against fungal infection. mBio. 2021;12(2):e03368-20.
Baltazar LM, Nakayasu ES, Sobreira TJP. Galectin-3 disorganizes the extracellular vesicle-associated fungal defensins and promotes the fungicidal activity of macrophages against Paracoccidioides brasiliensis. mBio. 2021;12(4):e01192-21.
Campos EG, Gabriel HB, Dutra GF. Extracellular vesicles from Sporothrix brasiliensis and Sporothrix schenckii clinical isolates differentially modulate human macrophage and neutrophil functions. Med Mycol. 2021;59(10):973–985.
Rafiq A, Sahu S, Jaiswal H. Extracellular vesicles from Aspergillus fumigatus induce immunomodulation via endocytosis in human neutrophils. Front Immunol. 2022;13:955359.
Adekunle AA, Johnson PB, Williams RD, Martinez LF, Kumar S, Gupta R. Synergistic effects of Aspergillus fumigatus extracellular vesicles with amphotericin B. Antimicrob Agents Chemother. 2024;68(5):e00123-24.
de Almeida JRF, Gabriel JHB, Rella A. Extracellular vesicles from Aspergillus fumigatus trigger a stress response in other A. fumigatus cultures. mBio. 2022;13(1):e03174-21.
Brennan K, Conery AL, Van Niel G. Methodological challenges in the study of extracellular vesicles: A focus on ultracentrifugation. Biochim Biophys Acta Gen Subj. 2022;1866(10):130198.
Zhang Y, Bi J, Huang J. A comprehensive review on recent advances in exosome isolation and characterization: Toward clinical applications. Trends Biotechnol. 2023;41(10):1330–1347.
Chen Y, Zhu Q, Cheng L. Exosome detection via aptamer-gated metal-organic frameworks. Anal Chem. 2021;93(6):3109–3116.
Yang X, Meng S, Liu Y. Recent progress of exosome isolation and peptide recognition-guided strategies for exosome research. Front Chem. 2023;11:1146931.
Joffe LS, Pseftogas A, Nimrichter L. Lectin-based approaches for the study of fungal glycoconjugates and extracellular vesicles. J Fungi (Basel). 2021;7(12):1032.
Mellott AJ, Thomas EK, Kuriakose AA. Imaging the delivery of cancer-derived extracellular vesicles to the bone marrow using intravital microscopy. J Extracell Vesicles. 2021;10(9):e12111.
Wu Z, Zou C, Zhang Y. Exosomal protein landscape of HBV-infected hepatocytes reveals their contribution to viral pathogenesis. J Extracell Vesicles. 2021;10(7):e12097.
Park S, Lee JW, Kim HJ. Engineered bacterial EVs as a platform for non-living vaccines. Nat Nanotechnol. 2024;19(3):321–330.
Logozzi M, Di Raimo R, Mizzoni D. The dark side of exosomes: The role of these vesicles in the complications of diseases. Int J Mol Sci. 2021;22(12):6543.
Bleackley MR, Dawson CS, Anderson MA. Extracellular vesicles from plants and fungi. Proteomics. 2019 Apr;19(8):e1800232. Available from: https://doi.org/10.1002/pmic.201800232
Wiklander OPB, Brennan MÁ, Lötvall J, Breakefield XO, El Andaloussi S. Advances in therapeutic applications of extracellular vesicles. Sci Transl Med. 2019;11(492):eaav8521. Available from: https://doi.org/10.1126/scitranslmed.aav8521
de Jong OG, Verhaar MC, Chen Y, Vader P, Gremmels H, Posthuma G, et al. Extracellular vesicles in organoid models: Opportunities and challenges. J Extracell Vesicles. 2020;9(1):1773927.
Liu Y, Zhang Q, Wang X. Probiotic EVs enhance gut barrier function and reduce inflammation. Gut Microbes. 2024;16(1):2297834.
Vader P, Mol EA, Pasterkamp G, Schiffelers RM. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016 Nov 15;106(Pt A):148–156.
Hermann S, Kuhlmann JD, Pezoldt J. Extracellular vesicles in organoid systems—State of the art and future perspectives. Int J Mol Sci. 2021;22(11):5614.