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Production of antimicrobial metabolites against pathogenic bacteria and yeasts by Fusarium oxysporum in submerged culture processes

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Abstract

The antimicrobial activity of the metabolites produced by Fusarium oxysporum PR-33 in submerged culture was evaluated against Gram-positive and Gram-negative bacteria and yeasts. Metabolites were determined by HPLC–DAD-MS/MS. An extract was obtained following the removal of mycelium by centrifugation and lyophilisation of the supernatant. The compounds in this extract demonstrated broad-spectrum antimicrobial action, with rates of inhibition between 60 and 80%, depending on the species and extract tested. The major compounds of the extracts were identified as fusarinolic acid and its isomer [56.9% flask extract (FE)] and 59.2% bioreactor extract (BE), dehydrofusaric acid (35.7% FE and 31.6% BE), and fusaric acid (6.5% FE and 1.1% BE). Fusaric acid has been shown to be responsible for antimicrobial activity. The cytotoxicity of the extracts was evaluated in culture of HEK-293 and SH-SY5Y animal cells and toxicity of these extracts was verified even in the lowest tested concentrations. Therefore, our results indicate that the compounds identified exhibit potential as antimicrobial agents.

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References

  1. Appelbaum PC (2012) 2012 and beyond: potential for the start of a second pre-antibiotic era? J Antimicrob Chemother 67:2062–2068. https://doi.org/10.1093/jac/dks213

    Article  CAS  PubMed  Google Scholar 

  2. Yu L, Wang Y, Su X et al (2020) Biodiversity, isolation and genome analysis of sulfamethazine-degrading bacteria using high-throughput analysis. Bioprocess Biosyst Eng 43:1521–1531. https://doi.org/10.1007/s00449-020-02345-1

    Article  CAS  PubMed  Google Scholar 

  3. Van Der Waaij D, Nord CE (2000) Development and persistence of multi-resistance to antibiotics in bacteria; an analysis and a new approach to this urgent problem. Int J Antimicrob Agents 16:191–197. https://doi.org/10.1016/S0924-8579(00)00227-2

    Article  PubMed  Google Scholar 

  4. De Boer W, Folman LB, Summerbell RC, Boddy L (2005) Living in a fungal world: impact of fungi on soil bacterial niche development. FEMS Microbiol Rev 29:795–811. https://doi.org/10.1016/j.femsre.2004.11.005

    Article  CAS  PubMed  Google Scholar 

  5. Conti R, Guimarães DO, Pupo MT (2012) Aprendendo com as interações da natureza: microrganismos simbiontes como fontes de produtos naturais bioativos. Cienc Cult 64:43–47. https://doi.org/10.21800/s0009-67252012000300014

    Article  Google Scholar 

  6. Wang M, Kornsakulkarn J, Srichomthong K et al (2019) Antimicrobial anthraquinones from cultures of the ant pathogenic fungus Cordyceps morakotii BCC 56811. J Antibiot (Tokyo) 72:141–147. https://doi.org/10.1038/s41429-018-0135-y

    Article  CAS  Google Scholar 

  7. Ganesh Kumar C, Mongolla P, Joseph J et al (2010) Activité antimicrobienne d’extraits d’isolats fongiques du sol et du fumier du parc national de Kaziranga, Assam, Inde. J Mycol Med 20:283–289. https://doi.org/10.1016/j.mycmed.2010.08.002

    Article  Google Scholar 

  8. Khan AA, Bacha N, Ahmad B et al (2014) Fungi as chemical industries and genetic engineering for the production of biologically active secondary metabolites. Asian Pac J Trop Biomed 4:859–870. https://doi.org/10.12980/APJTB.4.2014APJTB-2014-0230

    Article  CAS  Google Scholar 

  9. Dutreix L, Bernard C, Juin C et al (2018) Do raspberry extracts and fractions have antifungal or anti-adherent potential against Candida spp.? Int J Antimicrob Agents 52:947–953. https://doi.org/10.1016/j.ijantimicag.2018.08.020

    Article  CAS  PubMed  Google Scholar 

  10. Ren D, Zhao Y, Nie Y et al (2014) Chemical composition of Pleurotus eryngii polysaccharides and their inhibitory effects on high-fructose diet-induced insulin resistance and oxidative stress in mice. Food Funct 5:2609–2620. https://doi.org/10.1039/c3fo60640f

    Article  CAS  PubMed  Google Scholar 

  11. Manganyi MC, Regnier T, Olivier EI (2015) Antimicrobial activities of selected essential oils against Fusarium oxysporum isolates and their biofilms. South African J Bot 99:115–121. https://doi.org/10.1016/j.sajb.2015.03.192

    Article  CAS  Google Scholar 

  12. Hussain H, Drogies KH, Al-Harrasi A et al (2015) Antimicrobial constituents from endophytic fungus Fusarium sp. Asian Pacific J Trop Dis 5:186–189. https://doi.org/10.1016/S2222-1808(14)60650-2

    Article  CAS  Google Scholar 

  13. Tao S, Peng L, Beihui L et al (1998) Successive cultivation of Fusarium oxysporum on rice chaff for economic production of fibrinolytic enzyme. Bioprocess Eng 18:379–381. https://doi.org/10.1007/s004490050459

    Article  CAS  Google Scholar 

  14. Almeida ÉS, de Oliveira D, Hotza D (2017) Characterization of silver nanoparticles produced by biosynthesis mediated by Fusarium oxysporum under different processing conditions. Bioprocess Biosyst Eng 40:1291–1303. https://doi.org/10.1007/s00449-017-1788-9

    Article  CAS  PubMed  Google Scholar 

  15. Kuhad RC, Manchanda M, Singh A (1999) Hydrolytic potential of extracellular enzymes from a mutant strain of Fusarium oxysporum. Bioprocess Eng 20:133–135. https://doi.org/10.1007/s004490050571

    Article  CAS  Google Scholar 

  16. Gambato G, Todescato K, Pavão EM et al (2016) Evaluation of productivity and antioxidant profile of solid-state cultivated macrofungi Pleurotus albidus and Pycnoporus sanguineus. Bioresour Technol 207:46–51. https://doi.org/10.1016/J.BIORTECH.2016.01.121

    Article  CAS  PubMed  Google Scholar 

  17. Camassola M, da Rosa LO, Calloni R et al (2013) Secretion of laccase and manganese peroxidase by Pleurotus strains cultivate in solid-state using Pinus spp. sawdust. Brazilian J Microbiol 44:207–213. https://doi.org/10.1590/S1517-83822013005000006

    Article  CAS  Google Scholar 

  18. Rodrigues E, Mariutti LRB, Mercadante AZ (2013) Carotenoids and phenolic compounds from Solanum sessiliflorum, an unexploited amazonian fruit, and their scavenging capacities against reactive oxygen and nitrogen species. J Agric Food Chem 61:3022–3029. https://doi.org/10.1021/jf3054214

    Article  CAS  PubMed  Google Scholar 

  19. Schuh RS, Poletto É, Fachel FNS et al (2018) Physicochemical properties of cationic nanoemulsions and liposomes obtained by microfluidization complexed with a single plasmid or along with an oligonucleotide: Implications for CRISPR/Cas technology. J Colloid Interface Sci 530:243–255. https://doi.org/10.1016/j.jcis.2018.06.058

    Article  CAS  PubMed  Google Scholar 

  20. Zhang H, Sun X, Xu C (2016) Antimicrobial activity of endophytic fungus Fusarium sp. isolated from medicinal honeysuckle plant. Arch Biol Sci 68:25–30. https://doi.org/10.2298/ABS140401004Z

    Article  Google Scholar 

  21. Musavi SF, Balakrishnan RM (2014) A Study on the Antimicrobial Potentials of an Endophytic Fungus Fusarium oxysporum NFX 06. J Med Bioeng 3:162–166. https://doi.org/10.12720/jomb.3.3.162-166

    Article  Google Scholar 

  22. Bacon CW, Porter JK, Norred WP, Leslie JF (1996) Production of fusaric acid by Fusarium species. Appl Environ Microbiol 62:4039–4043. https://doi.org/10.1128/aem.62.11.4039-4043.1996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang H, Ng TB (1999) Pharmacological activities of fusaric acid (5-butylpicolinic acid). Life Sci 65:849–856. https://doi.org/10.1016/S0024-3205(99)00083-1

    Article  CAS  PubMed  Google Scholar 

  24. Hldaka H, Nagatsu T, Takeya K et al (1969) Fusaric acid, a hypotensive agent produced by fungi. J Antibiot (Tokyo) 22:228–230. https://doi.org/10.7164/antibiotics.22.228

    Article  Google Scholar 

  25. Li X, Zhang ZL, Wang HF (2017) Fusaric acid (FA) protects heart failure induced by isoproterenol (ISP) in mice through fibrosis prevention via TGF-β1/SMADs and PI3K/AKT signaling pathways. Biomed Pharmacother 93:130–145. https://doi.org/10.1016/j.biopha.2017.06.002

    Article  CAS  PubMed  Google Scholar 

  26. Sondergaard TE, Fredborg M, Oppenhagen Christensen AM et al (2016) Fast screening of antibacterial compounds from Fusaria. Toxins (Basel) 8:1–9. https://doi.org/10.3390/toxins8120355

    Article  CAS  Google Scholar 

  27. Li J, Sun W, Guo Z et al (2014) Fusaric acid modulates Type Three Secretion System of Salmonella enterica serovar Typhimurium. Biochem Biophys Res Commun 449:455–459. https://doi.org/10.1016/j.bbrc.2014.05.044

    Article  CAS  PubMed  Google Scholar 

  28. Gashgari R, Gherbawy Y, Ameen F, Alsharari S (2016) Molecular characterization and analysis of antimicrobial activity of endophytic fungi from medicinal plants in Saudi Arabia. Jundishapur J Microbiol 9:1–8. https://doi.org/10.5812/jjm.26157

    Article  CAS  Google Scholar 

  29. Tchoukoua A, Hasegawa R, Hendracipta KA et al (2018) Structure elucidation of new fusarielins from Fusarium sp. and their antimicrobial activity. Magn Reson Chem 56:32–36. https://doi.org/10.1002/mrc.4662

    Article  CAS  PubMed  Google Scholar 

  30. Shen HS, Shao S, Chen JC, Zhou T (2017) Antimicrobials from mushrooms for assuring food safety. Compr Rev Food Sci Food Saf 16:316–329. https://doi.org/10.1111/1541-4337.12255

    Article  PubMed  Google Scholar 

  31. Amalfitano C, Pengue R, Andolfi A et al (2002) HPLC analysis of fusaric acid, 9,10-dehydrofusaric acid and their methyl esters, toxic metabolites from weed pathogenic Fusarium species. Phytochem Anal 13:277–282. https://doi.org/10.1002/pca.648

    Article  CAS  PubMed  Google Scholar 

  32. Shinde SB, Deshmukh HV (2014) Estimation of fusaric acid from culture filtrate of Fusarium udum by thin layer chromatography. Asian J Bio Sci 9:251–254. https://doi.org/10.15740/has/ajbs/9.2/251-254

    Article  Google Scholar 

  33. Tung TT, Jakobsen TH, Dao TT et al (2017) Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors. Eur J Med Chem 126:1011–1020. https://doi.org/10.1016/j.ejmech.2016.11.044

    Article  CAS  PubMed  Google Scholar 

  34. Sheik Abdul N, Nagiah S, Chuturgoon AA (2016) Fusaric acid induces mitochondrial stress in human hepatocellular carcinoma (HepG2) cells. Toxicon 119:336–344. https://doi.org/10.1016/j.toxicon.2016.07.002

    Article  CAS  PubMed  Google Scholar 

  35. Mamur S, Ünal F, Yılmaz S et al (2020) Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid. Drug Chem Toxicol 43:149–157. https://doi.org/10.1080/01480545.2018.1499772

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 472153/2013-7 and 310255/2012-0), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS 16/2551-0000246-0), and Coordenação de Apoio de Pessoal de Nível Superior (CAPES3255/2013).

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Authors and Affiliations

  1. Laboratory of Enzymes and Biomass, Institute of Biotechnology, University of Caxias Do Sul, Caxias Do Sul, RS, Brazil

    Liliane Poleto, Letícia Osório da Rosa, Roselei Claudete Fontana & Marli Camassola

  2. Institute of Food Science and Technology (ICTA), Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Eliseu Rodrigues

  3. Gene Therapy Center, Hospital of Clinics of Porto Alegre, Federal University of Rio Grande Do Sul, Porto Alegre, RS, 90035-903, Brazil

    Édina Poletto & Guilherme Baldo

  4. Laboratory Molecular Diagnostic, Institute of Biotechnology, University of Caxias Do Sul, Caxias Do Sul, RS, Brazil

    Liliane Poleto & Suelen Paesi

  5. National Institute of Research of the Amazon (INPA), Manaus, AM, 69011-970, Brazil

    Ceci Sales-Campos

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Poleto, L., da Rosa, L.O., Fontana, R.C. et al. Production of antimicrobial metabolites against pathogenic bacteria and yeasts by Fusarium oxysporum in submerged culture processes. Bioprocess Biosyst Eng 44, 1321–1332 (2021). https://doi.org/10.1007/s00449-021-02538-2

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