Antiparasitics from Microorganisms

  • Nasib Singh
  • Pooja Devi Gautam
  • Puja Kumari Chauhan
  • Tanvir Kaur
  • Karan Singh
  • Joginder Singh
  • Sumit Singh Dagar
Part of the Environmental Chemistry for a Sustainable World book series (ECSW, volume 28)


Parasitic protozoa and helminth worms are major public health problems in many countries of the world, particularly in the tropical regions. Most of these infections are considered neglected tropical diseases by the World Health Organization and are responsible for significant mortality and morbidity in socioeconomically under-developed populations. Malaria, leishmaniasis, lymphatic filariasis, schistosomiasis, toxoplasmosis, amoebic dysentery, trypanosomiasis, Chagas’ disease and soil-transmitted helminthiasis are devastating diseases.

Here we review antiparasitic drugs and potential drug candidates derived from microorganisms. Avermectins, ivermectin, paromomycin and amphotericin B are microbial metabolites or semi-synthetic derivatives which remain the mainstay of antiparasitic chemotherapy. Among several species of bacteria and fungi, Streptomyces spp. are the most prolific producer of antiparasitic agents. Many microbially derived bioactive compounds have progressed in various phases of drug discovery and development phases and are expected to strengthen our current arsenal against parasitic diseases. The untapped microbial resources, i.e. marine, endophytic, endolichenic and extremophilic microbes, could afford novel leads for drug development against parasitic infections. In coming years, microbial bioprospecting, metagenomics, drug repurposing, genome mining, combinatorial chemistry supported by public–private partnerships and multidisciplinary collaborations are poised to accelerate the antiparasitic drug development process. Emphasis is also warranted on developing and utilizing high-throughput screening assays and novel target-based drug discovery approaches.


Parasitic protozoa Helminth parasites Cestodes Trematodes Nematodes Microorganisms Avermectins Streptomyces Ivermectin Drug development 



NS and KS are thankful to the Chancellor, Eternal University, Baru Sahib, Himachal Pradesh, for the constant support and infrastructural facilities.


  1. Agrawal S, Acharya D, Adholeya A, Barrow CJ, Deshmukh SK (2017) Nonribosomal peptides from marine microbes and their antimicrobial and anticancer potential. Front Pharmacol 8:828. CrossRefGoogle Scholar
  2. Andrews KT, Fisher G, Skinner-Adams TS (2014) Drug repurposing and human parasitic protozoan diseases. Int J Parasitol 4:95–111. CrossRefGoogle Scholar
  3. Balunas MJ, Linington RG, Tidgewell K, Fenner AM, Ureña LD, Togna GD, Kyle DE, Gerwick WH (2009) Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity. J Nat Prod 73:60–66. CrossRefGoogle Scholar
  4. Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J et al (2013) Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med 368:524–532. CrossRefGoogle Scholar
  5. Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR (2013) Marine natural products. Nat Prod Rep 30:237–323. CrossRefGoogle Scholar
  6. Brissow ER, da Silva IP, de Siqueira KA, Senabio JA, Pimenta LP, Januário AH, Magalhães LG, Furtado RA, Tavares DC, Junior PA, Santos JL (2017) 18-Des-hydroxy Cytochalasin: an antiparasitic compound of Diaporthe phaseolorum-92C, an endophytic fungus isolated from Combretum lanceolatum Pohl ex Eichler. Parasitol Res 12:1–8. CrossRefGoogle Scholar
  7. Burg RW, Miller BM, Baker EE, Birnbaum J, Currie SA, Hartman R, Kong YL, Monaghan RL, Olson G, Putter I, Tunac JB, Wallick H, Stapley EO, Oiwa R, Omura S (1979) Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. Antimicrob Agents Chemother 15:361–367CrossRefGoogle Scholar
  8. Calcul L, Waterman C, Ma WS, Lebar MD, Harter C, Mutka T, Morton L, Maignan P, Olphen AV, Kyle DE, Vrijmoed L (2013) Screening mangrove endophytic fungi for antimalarial natural products. Mar Drugs 11:5036–5050. CrossRefGoogle Scholar
  9. Campbell WC (2012) History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Curr Pharm Biotechnol 13:853–865. CrossRefGoogle Scholar
  10. Conlan JV, Khamlome B, Vongxay K, Elliot A, Pallant L et al (2012) Soil-transmitted helminthiasis in Laos: a community-wide cross-sectional study of humans and dogs in a mass drug administration environment. Am J Trop Med Hyg 86:624–634. CrossRefGoogle Scholar
  11. Cota BB, Tunes LG, Maia DN, Ramos JP, Oliveira DM, Kohlhoff M, Alves TM, Souza-Fagundes EM, Campos FF, Zani CL (2018) Leishmanicidal compounds of Nectria pseudotrichia, an endophytic fungus isolated from the plant Caesalpinia echinata (Brazilwood). Mem Inst Oswaldo Cruz 113:102–110. CrossRefGoogle Scholar
  12. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot (Tokyo) 62:5–16. CrossRefGoogle Scholar
  13. DNDi (2018) Drugs for neglected diseases initiative. Accessed Jan 2018
  14. Dube A, Gupta R, Singh N (2009) Reporter genes facilitating discovery of drugs targeting protozoan parasites. Trends Parasitol 25:432–439. CrossRefGoogle Scholar
  15. Elkhayat ES, Ibrahim SR, Mohamed GA, Ross SA (2016) Terrenolide S, a new antileishmanial butenolide from the endophytic fungus Aspergillus terreus. Nat Prod Res 30:814–820. CrossRefGoogle Scholar
  16. Espinosa A, Socha AM, Ryke E, Rowley DC (2012) Antiamoebic properties of the actinomycete metabolites echinomycin A and tirandamycin A. Parasitol Res 111:2473–2477. CrossRefGoogle Scholar
  17. Field MC, Horn D, Fairlamb AH, Ferguson MA, Gray DW, Read KD, De Rycker M, Torrie LS, Wyatt PG, Wyllie S, Gilbert IH (2017) Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nat Rev Microbiol 15:217–231. CrossRefGoogle Scholar
  18. GAHI (2017) Global atlas of helminth infections. London School of Hygiene and Tropical Medicine. Accessed 12 Dec 2017
  19. Gao J, Radwan MM, León F, Wang X, Jacob MR, Tekwani BL, Khan SI, Lupien S, Hill RA, Dugan FM, Cutler HG (2012) Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens. Med Chem Res 21:3080–3086. CrossRefGoogle Scholar
  20. GBD (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390:1211–1259. CrossRefGoogle Scholar
  21. Hotez PJ (2017) Ten failings in global neglected tropical diseases control. PLoS Negl Trop Dis 11:e0005896. CrossRefGoogle Scholar
  22. Hotez PJ, Damania A (2018) India’s neglected tropical diseases. PLoS Negl Trop Dis 12:e0006038. CrossRefGoogle Scholar
  23. Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118:1311–1121. CrossRefGoogle Scholar
  24. Isaka M, Jaturapat A, Kramyu J, Tanticharoen M, Thebtaranonth Y (2002) Potent in vitro antimalarial activity of metacycloprodigiosin isolated from Streptomyces spectabilis BCC 4785. Antimicrob Agents Chemother 46:1112–1113. CrossRefGoogle Scholar
  25. Iwatsuki M, Nishihara-Tsukashima A, Ishiyama A, Namatame M, Watanabe Y, Handasah S, Pranamuda H, Marwoto B, Matsumoto A, Takahashi Y, Otoguro K (2012) Jogyamycin, a new antiprotozoal aminocyclopentitol antibiotic, produced by Streptomyces sp. a-WM-JG-16.2. J Antibiot 65:169–171. CrossRefGoogle Scholar
  26. Kar S, Sharma G, Das PK (2011) Fucoidan cures infection with both antimony-susceptible and-resistant strains of Leishmania donovani through Th1 response and macrophage-derived oxidants. J Antimicrob Chemother 66:618–625. CrossRefGoogle Scholar
  27. Khare S et al (2016) Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness. Nature 537:229–233. CrossRefGoogle Scholar
  28. Krücken J, Harder A, Jeschke P, Holden-Dye L, O’Connor V, Welz C, von Samson-Himmelstjerna G (2012) Anthelmintic cyclooctadepsipeptides: complex in structure and mode of action. Trends Parasitol 28:385–394. CrossRefGoogle Scholar
  29. Kimura T, Iwatsuki M, Asami Y, Ishiyama A, Hokari R, Otoguro K et al (2016) Anti-trypanosomal compound, sagamilactam, a new polyene macrocyclic lactam from Actinomadura sp. K13-0306. J Antibiot 69:818. CrossRefGoogle Scholar
  30. Kumar M, Tripathi MK, Srivastava A, Gour JK, Singh RK, Tilak R, Asthana RK (2013) Cyanobacteria, Lyngbya aestuarii and Aphanothece bullosa as antifungal and antileishmanial drug resources. Asian Pac J Trop Biomed 3:458–463. CrossRefGoogle Scholar
  31. Lenta BN, Ngatchou J, Frese M, Ladoh-Yemeda F, Voundi S, Nardella F, Michalek C, Wibberg D, Ngouela S, Tsamo E, Kaiser M (2016) Purpureone, an antileishmanial ergochrome from the endophytic fungus Purpureocillium lilacinum. Z Naturforsch B 71:1159–1167. CrossRefGoogle Scholar
  32. Linington RG, Clark BR, Trimble EE, Almanza A, Ureña LD, Kyle DE, Gerwick WH (2009) Antimalarial peptides from marine cyanobacteria: isolation and structural elucidation of gallinamide A. J Nat Prod 72:14–17. CrossRefGoogle Scholar
  33. Lopes SC, Blanco YC, Justo GZ, Nogueira PA, Rodrigues FL, Goelnitz U, Wunderlich G, Facchini G, Brocchi M, Duran N, Costa FT (2009) Violacein extracted from Chromobacterium violaceum inhibits Plasmodium growth in vitro and in vivo. Antimicrob Agents Chemother 53:2149–2152. CrossRefGoogle Scholar
  34. Ma G, Khan SI, Jacob MR, Tekwani BL, Li Z, Pasco DS, Walker LA, Khan IA (2004) Antimicrobial and antileishmanial activities of hypocrellins A and B. Antimicrob Agents Chemother 48:4450–4452. CrossRefGoogle Scholar
  35. Manivasagan P, Venkatesan J, Sivakumar K, Kim SK (2014) Pharmaceutically active secondary metabolites of marine actinobacteria. Microbiol Res 169:262–278. CrossRefGoogle Scholar
  36. Malak LG, Ibrahim MA, Bishay DW, Abdel-Baky AM, Moharram AM, Tekwani B et al (2014) Antileishmanial metabolites from Geosmithia langdonii. J Nat Prod 77:1987–1991. CrossRefGoogle Scholar
  37. Martínez-Luis S, Della-Togna G, Coley PD, Kursar TA, Gerwick WH, Cubilla-Rios L (2008) Antileishmanial constituents of the Panamanian endophytic fungus Edenia sp. J Nat Prod 71:2011–2014. CrossRefGoogle Scholar
  38. McSorley HJ, Maizels RM (2012) Helminth infections and host immune regulation. Clin Micro Rev 25:585–608. CrossRefGoogle Scholar
  39. Molyneux DH, Savioli L, Engels D (2017) Neglected tropical diseases: progress towards addressing the chronic pandemic. Lancet 389:312–325. CrossRefGoogle Scholar
  40. Müller J, Hemphill A (2016) Drug target identification in protozoan parasites. Expert Opin Drug Discov 11:815–824. CrossRefGoogle Scholar
  41. Nagle AS, Khare S, Kumar AB, Supek F, Buchynskyy A, Mathison CJ, Chennamaneni NK, Pendem N, Buckner FS, Gelb MH, Molteni V (2014) Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis. Chem Rev 114:11305–11347. CrossRefGoogle Scholar
  42. Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79:629–661. CrossRefGoogle Scholar
  43. NVBDCP (2018) National vector borne disease control programme. Ministry of Health and Family Welfare, Govt. of India. Accessed 13 May 2018
  44. Omura S (2008) Ivermectin: 25 years and still going strong. Int J Antimicrob Agents 31:91–98. CrossRefGoogle Scholar
  45. Omura S, Shiomi K (2007) Discovery, chemistry, and chemical biology of microbial products. Pure Appl Chem 79:581–591. CrossRefGoogle Scholar
  46. Otoguro K, Ishiyama A, Namatame M, Nishihara A, Furusawa T, Masuma R, Shiomi K, Takahashi Y, Yamada H, Ōmura S (2008) Selective and potent in vitro antitrypanosomal activities of ten microbial metabolites. J Antibiot 61:372–378. CrossRefGoogle Scholar
  47. Partridge FA, Brown AE, Buckingham SD, Willis NJ, Wynne GM, Forman R, Else KJ, Morrison AA, Matthews JB, Russell AJ, Lomas DA, Sattelle DB (2018) An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. Int J Parasitol Drugs Drug Resist 8:8–21. CrossRefGoogle Scholar
  48. Pimentel-Elardo SM, Kozytska S, Bugni TS, Ireland CM, Moll H, Hentschel U (2010) Anti-parasitic compounds from Streptomyces sp. strains isolated from Mediterranean sponges. Mar Drugs 8:373–380. CrossRefGoogle Scholar
  49. Preston S, Gasser RB (2018) Working towards new drugs against parasitic worms in a public-development partnership. Trends Parasitol 34:4–6. CrossRefGoogle Scholar
  50. Prudhomme J, McDaniel E, Ponts N, Bertani S, Fenical W, Le Roch K (2008) Marine actinomycetes: a new source of compounds against the human malaria parasite. PLoS One 3:e2335. CrossRefGoogle Scholar
  51. Rahul S, Chandrashekhar P, Hemant B, Chandrakant N, Laxmikant S, Satish P (2014) Nematicidal activity of microbial pigment from Serratia marcescens. Nat Prod Res 28:1399–1404. CrossRefGoogle Scholar
  52. Rateb ME, Hallyburton I, Houssen WE, Bull AT, Goodfellow M, Santhanam R, Jaspars M, Ebel R (2013) Induction of diverse secondary metabolites in Aspergillus fumigatus by microbial co-culture. RSC Adv 3:14444–14450. CrossRefGoogle Scholar
  53. Robert-Gangneux F, Darde ML (2012) Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 25:264–296. CrossRefGoogle Scholar
  54. Rodrigues APD, Farias LHS, Carvalho ASC, Santos AS, do Nascimento JLM, Silva EO (2014) A novel function for kojic acid, a secondary metabolite from Aspergillus fungi, as antileishmanial agent. PLoS One 9:e91259. CrossRefGoogle Scholar
  55. da Silva IP, Brissow E, Kellner Filho LC, Senabio J, de Siqueira KA, Vandresen Filho S, Damasceno JL, Mendes SA, Tavares DC, Magalhães LG, Junior PA (2017) Bioactive compounds of Aspergillus terreus-F7, an endophytic fungus from Hyptis suaveolens (L.) Poit. World J Microbiol Biotechnol 33:62. CrossRefGoogle Scholar
  56. Silver ZA, Kaliappan SP, Samuel P, Venugopal S, Kang G, Sarkar R, Ajjampur SSR (2018) Geographical distribution of soil transmitted helminths and the effects of community type in South Asia and South East Asia – a systematic review. PLoS Negl Trop Dis 12:e0006153. CrossRefGoogle Scholar
  57. Simmons TL, Engene N, Ureña LD, Romero LI, Ortega-Barría E, Gerwick L, Gerwick WH (2008) Viridamides A and B, lipodepsipeptides with antiprotozoal activity from the marine cyanobacterium Oscillatoria nigro-viridis. J Nat Prod 71:1544–1550. CrossRefGoogle Scholar
  58. Singh N, Dube A (2015) Reporter genes in parasites. In: Mehlhorn H (ed) Encyclopedia of parasitology. Springer-Verlag, Berlin. Chapter No. 3511-1. Google Scholar
  59. Singh OP, Hasker E, Boelaert M, Sundar S (2016) Elimination of visceral leishmaniasis on the Indian subcontinent. Lancet Infect Dis pii:S1473-3099(16)30140-2. CrossRefGoogle Scholar
  60. Soares DC, Szlachta MM, Teixeira VL, Soares AR, Saraiva EM (2016) The brown alga Stypopodium zonale (Dictyotaceae): a potential source of anti-leishmania drugs. Mar Drugs 14:163. CrossRefGoogle Scholar
  61. Sorobetea D, Svensson-Frej M, Grencis R (2018) Immunity to gastrointestinal nematode infections. Mucosal Immunol 11:304–315. CrossRefGoogle Scholar
  62. Stutzer C, Richards SA, Ferreira M, Baron S, Maritz-Olivier C (2018) Metazoan parasite vaccines: present status and future prospects. Front Cell Infect Microbiol 8:67. CrossRefGoogle Scholar
  63. Sundar S, Chakravarty J (2010) Liposomal amphotericin B and leishmaniasis: dose and response. J Global Infect Dis 2:159–166. CrossRefGoogle Scholar
  64. Sundar S, Chakravarty J (2015) An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother 16:237–252. CrossRefGoogle Scholar
  65. Sundar S, Jha TK, Thakur CP et al (2007) Injectable paromomycin for visceral leishmaniasis in India. N Engl J Med 356:2571–2581. CrossRefGoogle Scholar
  66. Tchokouaha Yamthe LR, Appiah-Opong R, Tsouh Fokou PV, Tsabang N, Fekam Boyom F, Nyarko AK, Wilson MD (2017) Marine algae as source of novel antileishmanial drugs: a review. Mar Drugs 15:323. CrossRefGoogle Scholar
  67. Urban JF Jr, Hu Y, Miller MM, Scheib U, Yiu YY, Aroian RV (2013) Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. PLoS Negl Trop Dis 7:e2263. CrossRefGoogle Scholar
  68. Watts KR, Ratnam J, Ang KH, Tenney K, Compton JE, McKerrow J, Crews P (2010) Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi. Bioorg Med Chem 18:2566–2574. CrossRefGoogle Scholar
  69. WHO (2018) World Health Organization. Neglected tropical diseases. Accessed 13 May 2018

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Nasib Singh
    • 1
  • Pooja Devi Gautam
    • 2
  • Puja Kumari Chauhan
    • 2
  • Tanvir Kaur
    • 3
  • Karan Singh
    • 4
  • Joginder Singh
    • 5
  • Sumit Singh Dagar
    • 6
  1. 1.Department of Microbiology, Akal College of Basic SciencesEternal UniversityBaru SahibIndia
  2. 2.Department of Zoology, Akal College of Basic SciencesEternal UniversityBaru SahibIndia
  3. 3.Department of Biotechnology, Akal College of AgricultureEternal UniversityBaru SahibIndia
  4. 4.Department of Chemistry, Akal College of Basic SciencesEternal UniversityBaru SahibIndia
  5. 5.Department of BiotechnologyLovely Professional UniversityPhagwaraIndia
  6. 6.Bioenergy GroupAgharkar Research InstitutePuneIndia

Personalised recommendations