Microbial Endophytes: Their Resilience for Innovative Treatment Solution to Neglected Tropical Diseases

  • Ajay Kumar Verma
  • Saurabh Kumar Patel
  • Chandra Bhan Pratap
  • Mayank Gangwar
  • Gopal Nath


Fungal endophytes are relatively overlooked as a platform for discovering bioactive molecules against some major neglected tropical diseases, until some recent reports. Looking their potential as prolific producer of bioactive compounds against array of diseases and ailments makes them a suitable platform for such explorations. A major part of third world countries are facing growing problems of neglected tropical diseases (NTDs). More than two billion people of tropical and subtropical countries are facing serious health problems caused by lymphatic filariasis, onchocerciasis, echinococcosis, and other helminthic and zoonotic infections. Increasing side effects and appearance of resistance to the synthetic anthelmintics stimulates researchers for exploration of novel natural alternatives from medicinal plants and their associated endophytic microbes as a useful alternative. In this chapter, some aspects with respect to novel chemistry of endophytes and their structure activity relationship (SAR) toward tropical diseases like antiparasitic, antimalarial, and other neglected tropical diseases have been discussed.


High Performance Liquid Chromatography Endophytic Fungus Lymphatic Filariasis Tropical Disease Fungal Endophyte 


  1. Arnold A, Maynard Z, Gilbert G, Coley P, Kursar T (2000) Are tropical endophytes hyperdiverse? Ecol Lett 3:267–274CrossRefGoogle Scholar
  2. Arnold A, Maynard Z, Gilbert G (2001) Fungal endophytes in dicotyledonous neotropical trees: patterns of abundance and diversity. Mycol Res 105:1502–1507CrossRefGoogle Scholar
  3. Asford R (1997) The leishmaniases as model zoonoses. Ann Trop Med Parasitol 91:693–702CrossRefGoogle Scholar
  4. Baker D, Mocek U, Garr C (2000) Natural products vs. combinatorials: a case study. In: Wrigley SK, Hayes MA, Thomas R, Chrystal EJT, Nicholson N (eds) Biodiversity: new leads for pharmaceutical and agrochemical industries. The Royal Society of Chemistry, Cambridge, pp 66–72Google Scholar
  5. Barrios-González J, Mejia A (1996) Production of secondary metabolites by solid state fermentation. Biotechnol Ann Rev 2:83–121Google Scholar
  6. Campos F, Rosa L, Cota B, Caligiorne R, Rabello A, Alves T, Rosa C, Zani C (2008) Leishmanicidal metabolites from Cochliobolus sp., an endophytic fungus isolated from Piptadenia adiantoides (Fabaceae). PLoS Negl Trop Dis 2:348CrossRefGoogle Scholar
  7. Cao S, Clardy J (2011) New naphthoquinones and a new d-lactone produced by endophytic fungi from Costa Rica. Tetrahedron Lett 52:2206–2208PubMedCrossRefGoogle Scholar
  8. Cao S, Ross L, Tamayo G, Clardy J (2010) Asterogynins: secondary metabolites from a Costa Rican endophytic fungus. Org Lett 12:4661–4663PubMedCrossRefGoogle Scholar
  9. Carroll I, Toovey S, Van Gompel A (2007) Dengue fever and pregnancy-A review and comment. Travel Med Infect Dis 5:183–188PubMedCrossRefGoogle Scholar
  10. Carvalho CR, Gonçalves VN, Pereira CB, Johann S, Galliza IV, Alves TMA, Rabello A, Sobral MEG, Zani CL, Rosa CA, Rosa LH (2012) The diversity, antimicrobial and anticancer activity of endophytic fungi associated with the medicinal plant Stryphnodendron adstringens (Mart.) Coville (Fabaceae) from the Brazilian savannah. Symbiosis 57:95–107CrossRefGoogle Scholar
  11. Cota B, Rosa L, Caligiorne R, Rabello T, Rosa C, Zani C (2008) Altenusin, a biphenyl isolated from the endophytic fungus Alternaria sp. inhibits trypanothione reductase from Trypanosoma cruzi. FEMS Microbiol Lett 285:177–182PubMedCrossRefGoogle Scholar
  12. Croft S, Coombs G (2003) Leishmaniasis-current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19:502–508PubMedCrossRefGoogle Scholar
  13. Davis R, Carroll A, Andrews K, Boyle G, Tran T, Healy P, Kalaitzis J, Shivas R (2010) Pestalactams A–C: novel caprolactams from the endophytic fungus. Org Biomol Chem 8:1785–1790PubMedCrossRefGoogle Scholar
  14. Dreyfuss MM, Chapela IH (1994) Potential of fungi in the discovery of novel, low-molecular weight pharmaceuticals. In: Gullo VP (ed) The discovery of natural products with therapeutic potential. Butterworth-Heinemann, London, pp 49–80CrossRefGoogle Scholar
  15. Ganley R, Brunsfeld S, Newcombe G (2004) A community of unknown, endophytic fungi in western white pine. Proc Natl Acad Sci U S A 101:10107–10112PubMedCrossRefGoogle Scholar
  16. Gardner D, Ryman F (2010) Yellow fever: a reemerging threat. Clin Lab Med 30:237–260PubMedCrossRefGoogle Scholar
  17. Giridharan P, Verekar SA, Khanna A, Mishra PD, Deshmukh SK (2012) Anti-cancer activity of sclerotiorin, isolated from an endophytic fungus Cephalotheca faveolata Yaguchi, Nishim & Udagawa. Indian J Exp Biol 50:464–468PubMedGoogle Scholar
  18. Guimarães DO, Borges WS, Kawano CY, Ribeiro PH, Goldman GH, Nomizo A, Thiemann OH, Oliva G, Lopes NP, Pupo MT (2008) Biological activities from extracts of endophytic fungi isolated from Viguiera arenaria and Tithonia diversifolia. FEMS Immunol Med Microbiol 52:134–144PubMedCrossRefGoogle Scholar
  19. Gunatilaka A (2005) Natural products from plants-associated microorganisms: distribution, structural diversity, bioactivity, and applications of their occurrence. J Nat Prod 69:509–526CrossRefGoogle Scholar
  20. Gunatilaka AAL (2006) Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J Nat Prod 69:509–526PubMedCrossRefGoogle Scholar
  21. Hawksworth D (2004) Fungal diversity and its implications for genetic resource collections. Stud Mycol 50:9–18Google Scholar
  22. Hayes E (2010) Is it time for a new yellow fever vaccine? Vaccine 28:8073–8076PubMedCrossRefGoogle Scholar
  23. Hazalin NA, Ramasamy K, Lim SM, Cole AL, Majeed AB (2012) Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes) from Malaysian rainforest. Phytomedicine 19:609–617PubMedCrossRefGoogle Scholar
  24. Hemtasin C, Kanokmedhakul S, Kanokmedhakul K, Hahnvajanawong C, Soytong K, Prabpai S, Kongsaeree P (2011) Cytotoxic pentacyclic and tetracyclic Aromatic sesquiterpenes from Phomopsis archeri. J Nat Prod 74:609–613PubMedCrossRefGoogle Scholar
  25. Heukelbach J, Chichava O, Oliveira A, Häfner K, Walther F (2011) Interruption and defaulting of multidrug therapy against Leprosy: population-based study in Brazil’s savannah region. PLoS Negl Trop Dis 5:e1031PubMedCrossRefGoogle Scholar
  26. Hölker U, Hofer M, Lenz J (2004) Biotechnological advantages of laboratory-scale solid-state fermentation with fungi. Appl Microbiol Biotechnol 64:175–186PubMedCrossRefGoogle Scholar
  27. Hölker U, Hofer M, Lenz J (2005) Solid-state fermentation – are there any biotechnological advantages? Curr Opin Microbiol 8:301–306PubMedCrossRefGoogle Scholar
  28. Hotez P, Yamey G (2009) The evolving scope of neglected tropical diseases. PLoS Negl Trop Dis 3:e379CrossRefGoogle Scholar
  29. Hotez P, Stoever K, Fenwick A, Molyneux D, Savioli L (2006) The Lancet’s chronic diseases series. Lancet 367:563–564PubMedCrossRefGoogle Scholar
  30. Hotez P, Bottazzi M, Franco-Paredes C, Ault S, Periago M (2008) The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination. PLoS Negl Trop Dis 2:e300PubMedCrossRefGoogle Scholar
  31. Hotez P, Fenwick A, Savioli L, Molyneux D (2009) Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373:570–575CrossRefGoogle Scholar
  32. Huang Y, Wang J, Li G, Zheng Z, Su W (2001) Antitumor and antifungal activities in endophytic fungi isolated from pharmaceutical plants. FEMS Immunol Med Microbiol 31:163–167PubMedCrossRefGoogle Scholar
  33. Isaka M, Berkaew P, Intereya K, Komwijit S, Sathitkunanon T (2007) Antiplasmodial and antiviral cyclohexadepsipeptides from the endophytic fungus Pullularia sp. BCC 8613. Tetrahedron 63:6855–6860CrossRefGoogle Scholar
  34. Kontnik R, Clardy J (2008) Codinaeopsin, an antimalarial fungal polyketide. Org Lett 10:4149–4151PubMedCrossRefGoogle Scholar
  35. Larsen T, Smedgaard J, Nielsen K, Hansen M, Frisvad J (2005) Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Nat Prod Rep 22:672–695PubMedCrossRefGoogle Scholar
  36. Li M, Wu Y, Jiang F, Yu X, Tang K, Miao Z (2009) Isolation, identification and anticancer activity of an endophytic fungi from Juglans mandshurica. Zhongguo Zhong Yao Za Zhi 34:1623–1627PubMedGoogle Scholar
  37. Lieckfeldt E, Seifert KA (2000) An evaluation of the use of ITS sequences in the taxonomy of the hypocreales. Stud Mycol 45:35–44Google Scholar
  38. Lopes N, Albuquerque S, Kato M, Yoshida M (1998) Flavonoids and lignans from Virola surinamensis twigs and their in-vitro activity against Trypanosoma cruzi. Planta 64:667–669Google Scholar
  39. Marinho A, Rodrigues-Filho E, Moitinho M, Santos L (2005) Biologically active polyketides produced by Penicillium janthinellum isolated as an endophytic fungus from fruits of Melia azedarach. J Braz Chem Soc 16:280–283CrossRefGoogle Scholar
  40. Martínez-Luis S, Cherigo L (2012) Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus sp. strain F1544. Nat Prod Commun 7:165–168PubMedGoogle Scholar
  41. Martínez-Luis S, Cherigo L, Spadafora C, Gerwick W, Cubilla-Rios L (2009) Additional anti-leishmanial constituents of the Panamanian endophytic fungus Edenia sp. Revista Latinoamericana de Química 37:104–114Google Scholar
  42. Martínez-Luis S, Cherigo L, Higginbotham S, Arnold E, Spadafora C, Ibañez A, Gerwick WH, Cubilla-Rios L (2011) Screening and evaluation of antiparasitic and in-vitro anticancer activities of Panamanian endophytic fungi. Int Microbiol 14:95–102PubMedGoogle Scholar
  43. Martins R, Latone L, Sartorelli P, Kato M (2003) Trypanocidal tetrahydrofuran lignans from inflorescences of Piper solmsianum. Phytochemistry 64:667–670PubMedCrossRefGoogle Scholar
  44. Moreno E, Varughese T, Spadafora C, Arnold AE, Coley PD, Kursar TA, Gerwick WH, Cubilla-Rios L (2011) Chemical constituents of the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity. Nat Prod Commun 6:835–840PubMedGoogle Scholar
  45. Murrell S, Wu S, Butler M (2011) Review of dengue virus and the development of a vaccine. Biotechnol Adv 29:239–247PubMedCrossRefGoogle Scholar
  46. Pandey A (2003) Solid-state fermentation. Biochem Eng J 13:81–84CrossRefGoogle Scholar
  47. Petrini O (1991) Fungal endophytes of tree leaves. In: Andrews NJ, Hirano SS (eds) Microbial ecology of leaves. Springer, New York, pp 179–197CrossRefGoogle Scholar
  48. Petrini O, Sieber T, Toti L, Viret O (1992) Ecology metabolite production and substrate utilization in endophytic fungi. Nat Toxins 1:185–196PubMedCrossRefGoogle Scholar
  49. Porras-Alfaro A, Bayman P (2011) Hidden fungi, emergent properties: endophytes and microbiomes. Annu Rev Phytopathol 49:291–315PubMedCrossRefGoogle Scholar
  50. Promputtha I, Lumyong S, Dhanasekaran V, Huge E, Mackenzie C, Hyde K, Jeewon R (2007) Phylogenetic evaluation of whether endophytes become saprotrophs at host senescence. Microb Ecol 53:579–590PubMedCrossRefGoogle Scholar
  51. Raghukumar C, Nagarkar S, Raghukumar S (1992) Association of thraustochytrids and fungi with living marine algae. Mycol Res 96:542–546CrossRefGoogle Scholar
  52. Redline RC, Carris LM (1985) Endophytic fungi of grasses and woody plants. APS Press, St PaulGoogle Scholar
  53. Reyes P, Vallejo M (2005) Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection). Cochrane Database Syst Rev 1:1–16Google Scholar
  54. Robinson T, Singh D, Nigan P (2001) Solid-state fermentation: a promising microbial technology for secondary metabolites production. Appl Microbiol Biotechnol 55:284–289PubMedCrossRefGoogle Scholar
  55. Rodriguez S, Querol X, Alastues A, Kallos G, Kakaliagou O (2001) Saharan dust contribution to PM10 and TSP levels in southern and eastern Spain. Atmos Environ 35:2433–2447CrossRefGoogle Scholar
  56. Rodriguez RJ, White JF Jr, Arnold AE, Redman RS (2009) Fungal endophytes: diversity and functional roles. New Phytol 182:314–330PubMedCrossRefGoogle Scholar
  57. Schulz B, Boyle C, Draeger S, Römmert A, Krohn K (2002) Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol Res 106:996–1004CrossRefGoogle Scholar
  58. Silvia F, Sturdikova M, Muckova M (2007) Bioactive secondary metabolites produced by microorganisms associated with plants. Biologia 62:251–257CrossRefGoogle Scholar
  59. Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216PubMedCrossRefGoogle Scholar
  60. Strobel G (2002) Rainforest endophytes and bioactive products. Crit Rev Biotechnol 22:315–333PubMedCrossRefGoogle Scholar
  61. Strobel G (2003) Endophytes as sources of bioactive products. Microbes Infect 6:535–544CrossRefGoogle Scholar
  62. Strobel G (2006) Harnessing endophytes for industrial microbiology. Curr Opin Microbiol 9:240–244PubMedCrossRefGoogle Scholar
  63. Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502PubMedCrossRefGoogle Scholar
  64. Strobel GB, Daisy U, Castillo U, Harper J (2004) Natural products from endophytic microorganisms. J Nat Prod 67:257–268PubMedCrossRefGoogle Scholar
  65. Suryanarayanan S, Murali T, Venkatesan G (2002) Occurrence and distribution of fungal endophytes in tropical across a rainfall gradient. Can J Bot 80:818–826CrossRefGoogle Scholar
  66. Tan S, Chen X, Zhang A, Li D (2001) Isolation and characterization of DNA microsatellites from cotton bollworm (Helicoverpa armigera Hübner). Mol Ecol Notes 1:243–244CrossRefGoogle Scholar
  67. Tansuwan S, Pornpakakul S, Roengsumran S, Petsom A, Muangsin N, Sihanonta P, Chaichit N (2007) Antimalarial benzoquinones from an endophytic fungus Xylaria sp. J Nat Prod 70:1620–1623PubMedCrossRefGoogle Scholar
  68. Taylor J, Hyde K, Jones E (1999) Endophytic fungi associated with the temperate palm, Trachycarpus fortunei, within and outside its natural geographic range. New Phytol 142:335–346CrossRefGoogle Scholar
  69. Travassos L, Taborda C, Colombo A (2008) Treatment options for paracoccidioidomycosis and new strategies investigated. Exp Rev Anti Infect Ther 6:251–262CrossRefGoogle Scholar
  70. Umashankar R, Govindappa M, Ramachandra YL (2012) In-vitro antioxidant and anti-HIV activity of endophytic Coumarin from Crotalaria pallida Aiton. Planta Med 78:102CrossRefGoogle Scholar
  71. Verma VC, Kharwar RN, Strobel GA (2009) Chemical and functional diversity of natural products from plant associated fungal endophytes. Nat Prod Commun 4:1511–1532PubMedGoogle Scholar
  72. Verma VC, Gangwar M, Nath G (2013) Osmoregulatory and tegumental ultrastructural damages to protoscoleces of hydatid cysts Echinococcus granulosus induced by fungal endophytes. J Parasit Dis. doi: 10.1007/s12639-013-0271-z Google Scholar
  73. Verza M, Arakawa N, Lopes N, Kato M, Pupo M, Saida S, Carvalho I (2009) Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis sp. J Braz Chem Soc 20:195–200CrossRefGoogle Scholar
  74. Vrabcheva T, Usleber E, Dietrich R, Maertlbauer E (2000) Co-occurrence of ochratoxin A and citrinin in cereals from Bulgarian villages with a history of Balkan endemic nephropathy. J Agric Food Chem 48:2483–2488PubMedCrossRefGoogle Scholar
  75. World Health Organization (1991) Control of Chagas’ disease. WHO Technical report series No. 811. World Health Organization, GenevaGoogle Scholar
  76. World Health Organization (2006) Manuscript of neglected tropical diseases. Annual report. World Health Organization, GenevaGoogle Scholar
  77. Xu L, Zhou L, Zhao J, Li J, Li X, Wang J (2008) Fungal endophytes from Dioscorea zingiberensis rhizomes and their antibacterial activity. Lett Appl Microbiol 46:68–72PubMedCrossRefGoogle Scholar
  78. Zhang HW, Song YC, Tan RX (2006) Biology and chemistry of endophytes. Nat Prod Rep 23:753–771PubMedCrossRefGoogle Scholar
  79. Zhao J, Shan T, Mou Y, Zhao L (2011) Plant derived bioactive compounds produced by endophytic fungi. Mini Rev Med Chem 11:159–168PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Ajay Kumar Verma
    • 1
  • Saurabh Kumar Patel
    • 1
  • Chandra Bhan Pratap
    • 1
  • Mayank Gangwar
    • 1
    • 2
  • Gopal Nath
    • 1
  1. 1.Department of Microbiology, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of Pharmacology, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia

Personalised recommendations