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Enniatins from a marine-derived fungus Fusarium sp. inhibit biofilm formation by the pathogenic fungus Candida albicans

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Abstract

Candidemia is a life-threatening disease common in immunocompromised patients, and is generally caused by the pathogenic fungus Candida albicans. C. albicans can change morphology from yeast to hyphae, forming biofilms on medical devices. Biofilm formation contributes to the virulence and drug tolerance of C. albicans, and thus compounds that suppress this morphological change and biofilm formation are effective for treating and preventing candidemia. Marine organisms produce biologically active and structurally diverse secondary metabolites that are promising lead compounds for treating numerous diseases. In this study, we explored marine-derived fungus metabolites that can inhibit morphological change and biofilm formation by C. albicans. Enniatin B (1), B1 (2), A1 (3), D (4), and E (5), visoltricin (6), ergosterol peroxide (7), 9,11-dehydroergosterol peroxide (8), and 3β,5α,9α-trihydroxyergosta-7,22-dien-6-one (9) were isolated from the marine-derived fungus Fusarium sp. Compounds 1–5 and 8 exhibited inhibitory activity against hyphal formation by C. albicans, and compounds 1–3 and 8 inhibited biofilm formation by C. albicans. Furthermore, compounds 1–3 decreased cell surface hydrophobicity and expression of the hypha-specific gene HWP1 in C. albicans. Compound 1 was obtained in the highest yield. An in vivo evaluation system using silkworms pierced with polyurethane fibers (a medical device substrate) showed that compound 1 inhibited biofilm formation by C. albicans in vivo. These results indicate that enniatins could be lead compounds for therapeutic agents for biofilm infections by C. albicans.

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References

  1. Desai JV (2018) Candida albicans hyphae: from growth initiation to invasion. J Fungi 4:10. https://doi.org/10.3390/jof4010010

    Article  CAS  Google Scholar 

  2. Galia L, Pezzani MD, Compri M, Callegari A, Rajendran NB, Carrara E, Tacconelli E, the COMBACTE MAGNET EPI-Net Network (2022) Surveillance of antifungal resistance in candidemia fails to informantifungal stewardship in European countries. J Fungi 8:249. https://doi.org/10.3390/jof8030249

    Article  CAS  Google Scholar 

  3. Iyer KR, Robbins N, Cowen LE (2022) The role of Candida albicans stress response pathways in antifungaltolerance and resistance. iScience 25:103953. https://doi.org/10.1016/j.isci.2022.103953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kojic EM, Darouiche RO (2004) Candida infections of medical devices. Clin Microbiol Rev 17:255–267. https://doi.org/10.1128/CMR.17.2.255-267.2004

    Article  PubMed  PubMed Central  Google Scholar 

  5. Viudes A, Pemán J, Cantón E, Úbeda P, López-Ribot JL, Gobernado M (2002) Candidemia at a tertiary-care hospital: epidemiology, treatment, clinicaloutcome and risk factors for death. Eur J Clin Microbiol Infect Dis 21:767–774. https://doi.org/10.1007/s10096-002-0822-1

    Article  CAS  PubMed  Google Scholar 

  6. Finkel JS, Mitchell AP (2011) Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118. https://doi.org/10.1038/nrmicro2475

    Article  CAS  PubMed  Google Scholar 

  7. Kurakado S, Takatori K, Sugita T (2017) Minocycline inhibits Candida albicans budded-to-hyphal-form transition and biofilm formation. Jpn J Infect Dis 70:490–494. https://doi.org/10.7883/yoken.JJID.2016.369

    Article  CAS  PubMed  Google Scholar 

  8. Haga A, Tamoto H, Ishino M, Kimura E, Sugita T, Kinoshita K, Takahashi K, Shiro M, Koyama K (2013) Pyridone alkaloids from a marine-derived fungus, Stagonosporopsis cucurbitacearum, and their activities against azole-resistant Candida albicans. J Nat Prod 76:750–754. https://doi.org/10.1021/np300876t

    Article  CAS  PubMed  Google Scholar 

  9. Yamaguchi E, Okabe K, Kamauchi H, Kurakado S, Sugita T, Kinoshita K, Koyama K (2020) Antifungal compound against azole-resistant Candida albicans from a marine-derived fungus, Paraboeremia selaginellae. Heterocycles 100:645–652. https://doi.org/10.3987/COM-20-14229

    Article  CAS  Google Scholar 

  10. Ramage G, Walle KV, Wickes BL, López Ribot JL (2001) Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother 45:2475–2479. https://doi.org/10.1128/AAC.45.9.2475-2479.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhao LX, Li DD, Hu DD, Hu GH, Yan L, Wang Y, Jiang YY (2013) Effect of tetrandrine against Candida albicans biofilms. PLoS ONE 8:e79671. https://doi.org/10.1371/journal.pone.0079671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Matsumoto Y, Kurakado S, Sugita T (2021) Evaluating Candida albicans biofilm formation in silkworms. Med Mycol 59:201–205. https://doi.org/10.1093/mmy/myaa064

    Article  CAS  PubMed  Google Scholar 

  13. Visconti A, Blais LA, ApSimon JW, Greenhalgh R, Miller JD (1992) Production of enniatins by Fusarium acuminatum and Fusarium compactum in liquid culture: isolation and characterization of three new enniatins, B2, B3, and B4. J Agrie Food Chem 40:1076–1082. https://doi.org/10.1021/jf00018a034

    Article  CAS  Google Scholar 

  14. Blais LA, ApSimon JW, Blackwell BA, Greenhalgh R, Miller JD (1992) Isolation and characterization of enniatins from Fusariumavenaceum DAOM 196490. Can J Chem 70:1281–1287. https://doi.org/10.1139/v92-165

    Article  CAS  Google Scholar 

  15. Tomoda H, Nishida H, Huang XH, Masuma R, Kim YK, Omura S (1992) New cyclodepsipeptides, enniatins D, E and F produced by Fusarium sp. FO-1305. J Antibiot 45:1207–1215. https://doi.org/10.7164/antibiotics.45.1207

    Article  CAS  Google Scholar 

  16. Visconti A, Solfrizzo M (1994) Isolation, characterization and biological activity of visoltricin, a novel metabolite of Fusarium tricinctum. J Agrie Food Chem 42:195–199. https://doi.org/10.1021/jf00037a035

    Article  CAS  Google Scholar 

  17. Lee SH, Shim SH, Kim JS, Kang SS (2006) Constituents from the fruiting bodies of Ganoderma applanatum and their aldose reductase inhibitory activity. Arch Pharm Res 29:479–483. https://doi.org/10.1007/BF02969420

    Article  CAS  PubMed  Google Scholar 

  18. Parhira S, Zhu GY, Li T, Liu L, Bai LP, Jiang ZH (2016) Inhibition of IKK-β by epidioxysterols from the flowers of Calotropis gigantea (Niu jiao gua). Chin Med 11:9. https://doi.org/10.1186/s13020-016-0081-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xiong HY, Fei DQ, Zhou JS, Yang CJ, Ma GL (2009) Steroids and other constituents from the mushroom Armillaria lueo-virens. Chem Nat Compd 45:759–761. https://doi.org/10.1007/s10600-009-9456-1

    Article  CAS  Google Scholar 

  20. Prosperini A, Berrada H, Ruiz MJ, Caloni F, Coccini T, Spicer LJ, Perego MC, Lafranconi A (2017) A review of the mycotoxin enniatin B. Front Public Health 5:304. https://doi.org/10.3389/fpubh.2017.00304

    Article  PubMed  PubMed Central  Google Scholar 

  21. Meca G, Soriano JM, Gaspari A, Ritieni A, Moretti A, Mañes J (2010) Antifungal effects of the bioactive compounds enniatins A, A1, B, B1. Toxicon 56:480–485. https://doi.org/10.1016/j.toxicon.2010.04.013

    Article  CAS  PubMed  Google Scholar 

  22. Chen YK, Kuo YH, Chiang BH, Lo JM, Sheen LY (2009) Cytotoxic activities of 9,11-dehydroergosterol peroxide and ergosterol peroxide from the fermentation mycelia of ganoderma lucidum cultivated in the medium containing leguminous plants on Hep 3B cells. J Agric Food Chem 57:5713–5719

    Article  CAS  PubMed  Google Scholar 

  23. Vila TV, Ishida K, Souza W, Prousis K, Calogeropoulou T, Rozental S (2013) Effect of alkylphospholipids on Candida albicans biofilm formation and maturation. J Antimicrob Chemother 68:113–125. https://doi.org/10.1093/jac/dks353

    Article  CAS  PubMed  Google Scholar 

  24. Panagoda GJ, Ellepola AN, Samaranayake LP (1998) Adhesion to denture acrylic surfaces and relative cell-surface hydrophobicity of Candida parapsilosis and Candida albicans. APMIS 106:736–742. https://doi.org/10.1111/j.1699-0463.1998.tb00220.x

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Hiroaki Sasaki and Sanae Kurakado have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-Shi, Tokyo, 204-8588, Japan

    Hiroaki Sasaki, Yuta Yoshino, Kiyotaka Koyama & Kaoru Kinoshita

  2. Department of Microbiology, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-Shi, Tokyo, 204-8588, Japan

    Sanae Kurakado, Yasuhiko Matsumoto & Takashi Sugita

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  1. Hiroaki Sasaki
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  2. Sanae Kurakado
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  4. Yuta Yoshino
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Correspondence to Kaoru Kinoshita.

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Sasaki, H., Kurakado, S., Matsumoto, Y. et al. Enniatins from a marine-derived fungus Fusarium sp. inhibit biofilm formation by the pathogenic fungus Candida albicans. J Nat Med 77, 455–463 (2023). https://doi.org/10.1007/s11418-023-01684-z

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  • DOI: https://doi.org/10.1007/s11418-023-01684-z

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