Antiparasitics from Microorganisms
- 349 Downloads
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.
KeywordsParasitic 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.
- 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. https://doi.org/10.1007/s00436-017-5451-9 CrossRefGoogle Scholar
- 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
- 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. https://doi.org/10.4269/ajtmh.2012.11-0413 CrossRefGoogle Scholar
- 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. https://doi.org/10.1590/0074-02760170217 CrossRefGoogle Scholar
- DNDi (2018) Drugs for neglected diseases initiative. https://www.dndi.org/diseases-projects/. Accessed Jan 2018
- GAHI (2017) Global atlas of helminth infections. London School of Hygiene and Tropical Medicine. http://www.thiswormyworld.org/worms/. Accessed 12 Dec 2017
- 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. https://doi.org/10.1007/s00044-011-9798-7 CrossRefGoogle Scholar
- 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. https://doi.org/10.1016/S0140-6736(17)32154-2 CrossRefGoogle Scholar
- 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. https://doi.org/10.1038/ja.2011.136 CrossRefGoogle Scholar
- 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. https://doi.org/10.1515/znb-2016-0128 CrossRefGoogle Scholar
- 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. https://doi.org/10.1128/AAC.00693-08 CrossRefGoogle Scholar
- 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. https://doi.org/10.1021/cr500365f CrossRefGoogle Scholar
- NVBDCP (2018) National vector borne disease control programme. Ministry of Health and Family Welfare, Govt. of India. http://nvbdcp.gov.in/. Accessed 13 May 2018
- 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. https://doi.org/10.1016/j.ijpddr.2017.11.004 CrossRefGoogle Scholar
- 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. https://doi.org/10.1007/s11274-017-2228-3 CrossRefGoogle Scholar
- 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. https://doi.org/10.1371/journal.pntd.0006153 CrossRefGoogle Scholar
- WHO (2018) World Health Organization. Neglected tropical diseases. http://www.who.int/neglected_diseases/diseases/summary/en/. Accessed 13 May 2018