Skip to main content

Advertisement

SpringerLink
Log in

Mass Spectrometry Metabolomics Approach Reveals Anti-Trichomonas vaginalis Scaffolds from Marine Fungi

  • Original Article
  • Published:
Marine Biotechnology Aims and scope Submit manuscript

Abstract

Trichomoniasis is the most common non-viral sexually transmitted infection (STI) in the world caused by Trichomonas vaginalis. Failures in the treatment with the 5-nitroimidazole class including parasite resistance to metronidazole elicit new alternatives. Marine natural products are sources of several relevant molecules, presenting a variety of metabolites with numerous biological activities. In this work, we evaluated the anti-T. vaginalis activity of fungi associated with marine invertebrates by mass spectrometry-based metabolomics approaches. After screening of six marine fungi, extract from Penicillium citrinum FMPV 15 has shown to be 100% active against T. vaginalis, and the gel permeation column on Sephadex LH-20® yielded twelve organic fractions which five showed to be active. Metabolomics and statistical analyses were performed with all the samples (extract and fractions), and several compounds were suggested to be related to the activity. These components include citrinin, dicitrinin C, citreoisocoumarin, dihydrocitrinone, decarboxycitrinin, penicitrinone C, and others. The minimum inhibitory concentration (MIC) value of anti-T. vaginalis activity of citrinin was 200 µM. The marine fungi metabolites show potential as new alternatives to overcome drug resistance in T. vaginalis infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Dataset Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Alessio C, Nyirjesy P (2019) Management of resistant Trichomoniasis. Curr Infect Dis Rep 21:31

    Article  Google Scholar 

  • Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR (2015) Marine natural products. Nat Prod Rep 32:116–211

    Article  CAS  Google Scholar 

  • Blunt JW, Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR (2018) Marine natural products. Nat Prod Rep 35:8–53

    Article  CAS  Google Scholar 

  • Bouchemal K, Bories C, Loiseau PM (2017) Strategies for prevention and treatment of Trichomonas vaginalis infections. Clin Microbiol Rev 30:811–825

  • Braun D, Ezekiel CN, Marko D, Warth B (2020) Exposure to Mycotoxin-MixturesviaBreast milk: an ultra-sensitive LC-MS/MS biomonitoring approach. Front Chem 8:423

    Article  CAS  Google Scholar 

  • Chen G, Wang HF, Pei YH (2014) Secondary metabolites from marine-derived microorganisms. J Asian Nat Prod Res 16:105–122

    Article  CAS  Google Scholar 

  • Chen L, Zhao Y, Lan RF, Du L, Wang BS, Zhou T, Li YP, Zhang QQ, Ying MG, Zheng QH, Liu QY (2017) Dicitrinone D, an antimitotic polyketide isolated from the marine-derived fungus Penicillium citrinum. Tetrahedron 73:5900–5911

    Article  CAS  Google Scholar 

  • Clark BR, Capon RJ, Lacey E, Tennant S, Gill JH (2006) Citrinin revisited: from monomers to dimers and beyond. Org Biomol Chem 4:1520–1528

    Article  CAS  Google Scholar 

  • De Oliveira Filho JWG, Islam MT, Ali ES, Uddin SJ, Santos JVO, Alencar MVOB, Júnior ALG, Paz MFCJ, Brito MRM, Sousa JMC, Shaw S, Medeiros MGF, Dantas SMMM, Rolim HML, Ferreira PMP, Kamal MA, Pieczynska MD, Das N, Gupta VK, Mocan A, Andrade TJAS, Singh BN, Mishra SK, Atanashov AG, Melo-Cavalcante AAC (2017) A comprehensive review on biological properties of citrinin. Food Chem Toxicol 110:130–141

    Article  Google Scholar 

  • Dembogurski DSO, Trentin DS, Boareto AG, Rigo GV, Silva RC, Tasca T, Macedo AJ, Carollo CA, Silva DB (2018) Brown propolis-metabolomic innovative approach to determine compounds capable of killing Staphylococcus aureus biofilm and Trichomonas vaginalis. Food Res Int 111:661–673

    Article  Google Scholar 

  • Diamond LS (1957) The establishment of various trichomonads of animals and man in axenic cultures. J Parasitol 43:488–490. (PMID: 13463700)

    Article  CAS  Google Scholar 

  • Egbuta MA, Mwanza M, Babalola OO (2017) Health risks associated with exposure to filamentous fungi. Int J Environ Res Public Health 14:719

  • Estrella-Parra EA, Arreola R, Álvarez-Sánchez ME, Torres-Romero JC, Rojas-Espinosa O, De la Cruz-Santiago JA, Martinez-Benitez MB, López-Camarillo CL, Lara-Riegos JC, Arana-Argáez VE, Ramírez-Camacho MA (2022) Natural marine products as antiprotozoal agents against amitochondrial parasites. Int J Parasitol Drugs Drug Resist 19:40–46

  • European Food Safety Authority—panel on contaminants in the food chain (CONTAM) (2012) Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA J 10:2605

    Google Scholar 

  • Giordani RB, Vieira Pde B, Weizenmann M, Rosemberg DB, Souza AP, Bonorino C, De Carli GA, Bogo MR, Zuanazzi JA, Tasca T (2010) Candimine-induced cell death of the amitochondriate parasite Trichomonas vaginalis. J Nat Prod 73:2019–2023

  • Giordani RB, Vieira Pde B, Weizenmann M, Rosemberg DB, Souza AP, Bonorino C, De Carli GA, Bogo MR, Zuanazzi JA, Tasca T (2011) Lycorine induces cell death in the amitochondriate parasite, Trichomonas vaginalis, via an alternative non-apoptotic death pathway. Phytochemistry 72:645–650

    Article  CAS  Google Scholar 

  • González AM et al (1998) Estudio de la actividad hemolítica in vitro de extractos de hongos productores de citrinina. Revista Fabicibi, v.2, p. 127–130

  • Graça AP, Bondoso J, Gaspar H, Xavier JR, Monteiro MC, Cruz M, Oves-Costales D, Vicente F, Lage OM (2013) Antimicrobial activity of heterotrophic bacterial communities from the marine sponge Erylus discophorus (Astrophorida, Geodiidae). PLoS ONE 8:789–792

    Article  Google Scholar 

  • Gromski PS, Muhamadali H, Ellis DI, Xu Y, Correa E, Turner ML, Goodacre R (2015) A tutorial review: metabolomics and partial least squares-discriminant analysis–a marriage of convenience or a shotgun wedding. Anal Chim Acta 879:10–23

    Article  CAS  Google Scholar 

  • Guo W, Yang J, Niu X, Tangni EK, Zhaoa Z, Han Z (2021) A reliable and accurate UHPLC-MS/MS method for screening of Aspergillus, Penicillium and Alternaria mycotoxins in orange, grape and apple juices. Anal Methods 13:192–201

    Article  CAS  Google Scholar 

  • He Y, Cox RJ (2016) The molecular steps of citrinin biosynthesis in fungi. Chem Sci 7:2119–2127

    Article  CAS  Google Scholar 

  • Helber SB, Hoeijmakers DJJ, Muhando CA, Rohde S, Schupp PJ (2018) Sponge chemical defenses are a possible mechanism for increasing sponge abundance on reefs in Zanzibar. PLoS ONE 13:e0197617

    Article  Google Scholar 

  • Hirt RP, Sherrard J (2015) Trichomonas vaginalis origins, molecular pathobiology and clinical considerations. Curr Opin Infect Dis 28:72–79

    Article  CAS  Google Scholar 

  • Houbraken JAMP, Frisvad JC, Samson RA (2010) Taxonomy of Penicillium citrinum and related species. Fungal Diversity 44:117–133

    Article  Google Scholar 

  • Khalifa SAM, Elias N, Farag MA, Chen L, Saeed A, Hegazy MF, Moustafa MS, Abd El-Wahed A, Al-Mousawi SM, Musharraf SG, Chang FR, Iwasaki A, Suenaga K, Alajlani M, Göransson U, El-Seedi HR (2019) Marine natural products: a source of novel anticancer drugs. Mar Drugs 17:491

  • Liu Z, Frank M, Yu X, Yu H, Tran-Cong NM, Gao Y, Proksch P (2020) Secondary metabolites from marine-derived fungi from China. Prog Chem Org Nat Prod 111:81–153

    PubMed  Google Scholar 

  • Loges LA, Silva DB, Paulino GVB, Landell MF, Macedo AJ (2020) Polyketides from marine-derived Aspergillus welwitschiae inhibit Staphylococcus aureus virulence factors and potentiate vancomycin antibacterial activity in vivo. Microb Pathog 143:104066

    Article  CAS  Google Scholar 

  • Lu Z-Y, Lin Z-J, Wang W-L, Du L, Zhu T-J, Fang Y-C, Gu Q-Q, Zhu W-M (2008) Citrinin dimers from the halotolerant fungus Penicillium citrinum B-57. J Nat Prod 71:543–546

    Article  CAS  Google Scholar 

  • Menezes CB, Frasson AP, Tasca T (2016) Trichomoniasis—are we giving the deserved attention to the common non-viral sexually transmitted disease worldwide? Microb Cell 3:404–419

  • Masha SC, Cools P, Sanders EJ, Vaneechoutte M, Crucitti T (2019) Trichomonas vaginalis and HIV infection acquisition: a systematic review and meta-analysis. Sex Transm Infect 95:36–42

    Article  Google Scholar 

  • Newman DJ, Cragg GM (2016) Natural products as source of new drugs from 1981 to 2014. J Nat Prod 79:629–661

    Article  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83:770–803

    Article  CAS  Google Scholar 

  • Nielsen KF, Smedsgaard J (2003) Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography–UV–mass spectrometry methodology. J Chromatogr A 1002:111–136

    Article  CAS  Google Scholar 

  • Pailassa J, Maitre E, Troussard X (2022) Hairy cell leukemia (HCL) and HCL variant: updates and spotlights on therapeutic advances. Curr Oncol Rep (in Press). https://doi.org/10.1007/s11912-022-01285-1

    Article  Google Scholar 

  • Paulino GVB, Felix CR, Landell MF (2020) Diversity of filamentous fungi associated with coral and sponges in coastal reefs of northeast Brazil. J Basic Microbiol 60:103–111

    Article  CAS  Google Scholar 

  • Petersen LE, Kellermann MY, Schupp PJ (2020) In: Jungblut S, Liebich V, Bode-Dalby M (eds) Secondary metabolites of marine microbes: from natural products chemistry to chemical ecology. YOUMARES 9 - The Oceans: Our Research, Our Future. Springer. https://doi.org/10.1007/978-3-030-20389-4_8

  • Rigo GV, Frank LA, Galego GB, Santos ALS, Tasca T (2022) Novel treatment approaches to combat Trichomoniasis, a neglected and sexually transmitted infection caused by Trichomonas vaginalis: translational perspectives. Venereology 1:47–80

  • Rowley J, Vander Hoorn S, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, Chico RM, Smolak A, Newman L, Gottlieb S, Thwin SS, Broutet N, Taylor MM (2019) Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ 97:548–562

    Article  Google Scholar 

  • Salendra L, Lin X, Chen W, Pang W, Luo X, Long J, Liao S, Wang J, Zhou X, Liu Y, Yang B (2021) Cytotoxicity of polyketides and steroids isolated from the sponge-associated fungus Penicillium citrinum SCSIO 41017. Nat Prod Res 35:900–908

    Article  CAS  Google Scholar 

  • Scopel M, Santos O, Frasson AP, Abraham WR, Tasca T, Henriques AT, Macedo AJ (2013) Anti-Trichomonas vaginalis activity of marine-associated fungi from the South Brazilian Cost. Exp Parasitol 133:211–216

    Article  Google Scholar 

  • Senger FR, Campos-Silva R, Landell MF, Silva DB, Menezes CB, Rigo GV, Silva LN, Trentin DS, Macedo AJ, Tasca T (2022) Anti-Trichomonas vaginalis activity and chemical analysis of metabolites produced by marine-associated fungi. Parasitol Res (in Press). https://doi.org/10.1007/s00436-022-07442-6

    Article  Google Scholar 

  • Shinde P, Banerjee P, Mandhare A (2019) Marine natural products as source of new drugs: a patent review (2015–2018). Expert Opin Ther Pat 29:283–309

  • Sun W, Wu W, Liu X, Zaleta-Pinet DA, Clark BR (2019) Bioactive compounds isolated from marine-derived microbes in China: 2009–2018. Mar Drugs 17:339

  • Trisuwan K, Rukachaisirikul V, Borwornwiriyapan K, Phongpaichit S, Sakayaroj J (2014) Benzopyranone, benzophenone, and xanthone derivatives from the soil fungus Penicillium citrinum PSU-RSPG95. Tetrahedron Lett 55:1336–1338

    Article  CAS  Google Scholar 

  • Vieira PB, Silva NLF, Menezes CB, da Silva MV, Silva DB, Lopes NP et al (2017) Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula. PLoS ONE 12:e0188531

    Article  Google Scholar 

  • Wang YN, Meng LH, Wang BG (2020) Progress in research on bioactive secondary metabolites from deep-sea derived microorganisms. Mar Drugs 18:614

  • Weber JI, Rigo GV, Rocha DA, Fortes IS, Seixas A, de Andrade SF, Tasca T (2021) Modulation of peptidases by 2,4-diamine-quinazoline derivative induces cell death in the amitochondriate parasite Trichomonas vaginalis. Biomed Pharmacother 139:111611

  • Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA (2021) Sexually Transmitted Infections Treatment Guidelines, MMWR Recomm Rep 70:1–187

  • Yurchenko AN, Girich EV, Yurchenko EA (2021) Metabolites of marine sediment-derived fungi: actual trends of biological activity studies. Mar Drugs 19:88

  • Zain ul Arifeen M, Ma YN, Xue YR, Liu CH (2019) Deep-sea fungi could be the new arsenal for bioactive molecules. Mar Drugs 18:9

  • Zhang H, Ahima J, Yang Q, Zhao L, Zhang X, Zheng X (2021) A review on citrinin: Its occurrence, risk implications, analytical techniques, biosynthesis, physiochemical properties and control. Food Res Int 141:110075

Download references

Acknowledgements

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil) Marine Biotechnology Program (Rede MarAtivo, grants #408578/2013-0 and #408718/2013–7) and Universal 2018 (#428538/2018-5), and by the Fundação de Apoio à Pesquisa do Estado do Rio Grande do Sul (FAPERGS/Brazil) PRONEM-FAPERGS grant 16/2551-0000244-4. M.F.L. (grant 311553/2018–4), D.B.S. (grant 313047/2020-0), A.J.M. (grant 304014/2019-2), T.T. (grant 309764/2021-1), thank CNPq for researcher fellowships.

Author information

Authors and Affiliations

  1. Faculdade de Farmácia and Centro de Biotecnologia, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil

    Carla Teresinha Endres, Graziela Vargas Rigo, Luciana Angelo Loges, Alexandre José Macedo & Tiana Tasca

  2. Laboratório de Diversidade Molecular, Universidade Federal de Alagoas, Maceió, Alagoas, Brazil

    Melissa Fontes Landell

  3. Laboratório de Produtos Naturais E Espectrometria de Massas (LaPNEM), Faculdade de Ciências Farmacêuticas, Alimentos E Nutrição (FACFAN), Universidade Federal de Mato Grosso Do Sul, Mato Grosso Do Sul, Campo Grande, Brazil

    Denise Brentan Silva

Authors
  1. Carla Teresinha Endres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Graziela Vargas Rigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luciana Angelo Loges
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Melissa Fontes Landell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Denise Brentan Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexandre José Macedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tiana Tasca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandre José Macedo.

Ethics declarations

Competing Interests

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 413 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Endres, C.T., Rigo, G.V., Loges, L.A. et al. Mass Spectrometry Metabolomics Approach Reveals Anti-Trichomonas vaginalis Scaffolds from Marine Fungi. Mar Biotechnol 24, 1014–1022 (2022). https://doi.org/10.1007/s10126-022-10164-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10126-022-10164-6

Keywords

Search

Navigation