1921
Volume 101, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Strongyloidiasis, caused by infection, is an important neglected tropical disease that causes significant public health problems in the tropics and subtropics. The disease can persist in hosts for decades and may be life-threatening because of hyperinfection and dissemination. Ivermectin (mostly) and albendazole are the most common anthelmintics used for treatment. Albendazole is suboptimal for this parasite, and although ivermectin is quite effective in immunocompromised patients, a multiple-course regimen is required. Furthermore, reliance on a single drug class for treating intestinal nematodes is a recipe for future failure. Therefore, it is important to discover new anthelmintics to treat or prevent human strongyloidiasis. One promising candidate is the crystal protein Cry5B. Cry5B is highly potent against parasitic nematodes, for example, hookworms and . Here, we investigated the potential of Cry5B against . Multiple stages of , including the first larval stage (L1s), infective stage (iL3s), free-living adult stage, and parasitic female stage, were all susceptible to Cry5B as indicated by impairment of motility and decreased viability in vitro. In summary, Cry5B demonstrated strong potential as an effective anthelmintic for treatment and transmission control of human strongyloidiasis, justifying further experiments to investigate in vivo therapeutic efficacy.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.19-0083
2019-09-16
2020-09-26
Loading full text...

Full text loading...

/deliver/fulltext/14761645/101/5/tpmd190083.html?itemId=/content/journals/10.4269/ajtmh.19-0083&mimeType=html&fmt=ahah

References

  1. Greaves D, Coggle S, Pollard C, Aliyu SH, Moore EM, 2013. Strongyloides stercoralis infection. BMJ 347: f4610.
    [Google Scholar]
  2. Luvira V, Watthanakulpanich D, Pittisuttithum P, 2014. Management of Strongyloides stercoralis: a puzzling parasite. Int Health 6: 273281.
    [Google Scholar]
  3. Schar F, Trostdorf U, Giardina F, Khieu V, Muth S, Marti H, Vounatsou P, Odermatt P, 2013. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis 7: e2288.
    [Google Scholar]
  4. Prendki V, Fenaux P, Durand R, Thellier M, Bouchaud O, 2011. Strongyloidiasis in man 75 years after initial exposure. Emerg Infect Dis 17: 931932.
    [Google Scholar]
  5. Buonfrate D, Requena-Mendez A, Angheben A, Munoz J, Gobbi F, Van Den Ende J, Bisoffi Z, 2013. Severe strongyloidiasis: a systematic review of case reports. BMC Infect Dis 13: 78.
    [Google Scholar]
  6. Croker C, Reporter R, Redelings M, Mascola L, 2010. Strongyloidiasis-related deaths in the United States, 1991–2006. Am J Trop Med Hyg 83: 422426.
    [Google Scholar]
  7. Marcos LA, Terashima A, Canales M, Gotuzzo E, 2011. Update on strongyloidiasis in the immunocompromised host. Curr Infect Dis Rep 13: 3546.
    [Google Scholar]
  8. WHO, 2011. Helminth Control in School-Age Children. A Guide for Managers of Control Programmes. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/neglected_diseases/resources/9789241548267/en/.
    [Google Scholar]
  9. WHO, 2012. Research Priorities for Helminth Infections. WHO Technical Report Series. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/handle/10665/75922.
    [Google Scholar]
  10. Gupta S, Jain A, Fanning TV, Couriel DR, Jimenez CA, Eapen GA, 2006. An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: a case report. BMC Cancer 6: 87.
    [Google Scholar]
  11. Hunter CJ, Petrosyan M, Asch M, 2008. Dissemination of Strongyloides stercoralis in a patient with systemic lupus erythematosus after initiation of albendazole: a case report. J Med Case Rep 2: 156.
    [Google Scholar]
  12. Kaplan RM, Klei TR, Lyons ET, Lester G, Courtney CH, French DD, Tolliver SC, Vidyashankar AN, Zhao Y, 2004. Prevalence of anthelmintic resistant cyathostomes on horse farms. J Am Vet Med Assoc 225: 903910.
    [Google Scholar]
  13. Beknazarova M, Whiley H, Ross K, 2016. Advocating for both environmental and clinical approaches to control human strongyloidiasis. Pathogens 5: E59.
    [Google Scholar]
  14. Bravo A, Likitvivatanavong S, Gill SS, Soberon M, 2011. Bacillus thuringiensis: a story of a successful bioinsecticide. Insect Biochem Mol Biol 41: 423431.
    [Google Scholar]
  15. Ibrahim MA, Griko N, Junker M, Bulla LA, 2010. Bacillus thuringiensis: a genomics and proteomics perspective. Bioeng Bugs 1: 3150.
    [Google Scholar]
  16. Wei JZ, Hale K, Carta L, Platzer E, Wong C, Fang SC, Aroian RV, 2003. Bacillus thuringiensis crystal proteins that target nematodes. Proc Natl Acad Sci USA 100: 27602765.
    [Google Scholar]
  17. Cappello M, Bungiro RD, Harrison LM, Bischof LJ, Griffitts JS, Barrows BD, Aroian RV, 2006. A purified Bacillus thuringiensis crystal protein with therapeutic activity against the hookworm parasite Ancylostoma ceylanicum. Proc Natl Acad Sci USA 103: 1515415159.
    [Google Scholar]
  18. Hu Y, Zhan B, Keegan B, Yiu YY, Miller MM, Jones K, Aroian RV, 2012. Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms. PLoS Negl Trop Dis 6: e1900.
    [Google Scholar]
  19. Hu Y et al., 2018. Bacillus thuringiensis Cry5B protein as a new pan-hookworm cure. Int J Parasitol Drugs Drug Resist 8: 287294.
    [Google Scholar]
  20. 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.
    [Google Scholar]
  21. Hu Y, Georghiou SB, Kelleher AJ, Aroian RV, 2010. Bacillus thuringiensis Cry5B protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice. PLoS Negl Trop Dis 4: e614.
    [Google Scholar]
  22. Li X-Q, Tan A, Voegtline M, Bekele S, Chen C-S, Aroian RV, 2008. Expression of Cry5B protein from Bacillus thuringiensis in plant roots confers resistance to root-knot nematode. Biol Control 47: 97102.
    [Google Scholar]
  23. Hu Y, Platzer EG, Bellier A, Aroian RV, 2010. Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility. Proc Natl Acad Sci USA 107: 59555960.
    [Google Scholar]
  24. Hu Y, Miller M, Zhang B, Nguyen TT, Nielsen MK, Aroian RV, 2018. In vivo and in vitro studies of Cry5B and nicotinic acetylcholine receptor agonist anthelmintics reveal a powerful and unique combination therapy against intestinal nematode parasites. PLoS Negl Trop Dis 12: e0006506.
    [Google Scholar]
  25. Charuchaibovorn S, Sanprasert V, Nuchprayoon S, 2019. The experimental infections of the human isolate of Strongyloides stercoralis in a rodent model (The Mongolian gerbil, Meriones unguiculatus). Pathogens 8: E21.
    [Google Scholar]
  26. Koga K, Kasuya S, Khamboonruang C, Sukhavat K, Ieda M, Takatsuka N, Kita K, Ohtomo H, 1991. A modified agar plate method for detection of Strongyloides stercoralis. Am J Trop Med Hyg 45: 518521.
    [Google Scholar]
  27. Nolan TJ, Megyeri Z, Bhopale VM, Schad GA, 1993. Strongyloides stercoralis: the first rodent model for uncomplicated and hyperinfective strongyloidiasis, the Mongolian gerbil (Meriones unguiculatus). J Infect Dis 168: 14791484.
    [Google Scholar]
  28. Albarqi MM, Stoltzfus JD, Pilgrim AA, Nolan TJ, Wang Z, Kliewer SA, Mangelsdorf DJ, Lok JB, 2016. Regulation of life cycle checkpoints and developmental activation of infective larvae in Strongyloides stercoralis by dafachronic acid. PLoS Pathog 12: e1005358.
    [Google Scholar]
  29. Ashton FT, Zhu X, Boston R, Lok JB, Schad GA, 2007. Strongyloides stercoralis: amphidial neuron pair ASJ triggers significant resumption of development by infective larvae under host-mimicking in vitro conditions. Exp Parasitol 115: 9297.
    [Google Scholar]
  30. Stoltzfus JD, Massey HC Jr., Nolan TJ, Griffith SD, Lok JB, 2012. Strongyloides stercoralis age-1: a potential regulator of infective larval development in a parasitic nematode. PLoS One 7: e38587.
    [Google Scholar]
  31. Bischof LJ, Huffman DL, Aroian RV, 2006. C. elegans: Methods and Applications. Strange K, ed. Methods in Molecular Biology. Totowa, NJ: © Humana Press Inc.
    [Google Scholar]
  32. Bischof LJ, Huffman DL, Aroian RV, 2006. Assays for toxicity studies in C. elegans with Bt crystal proteins. Methods Mol Biol 351: 139154.
    [Google Scholar]
  33. Los FC, Kao CY, Smitham J, McDonald KL, Ha C, Peixoto CA, Aroian RV, 2011. RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin. Cell Host Microbe 9: 147157.
    [Google Scholar]
  34. Griffitts JS, Haslam SM, Yang T, Garczynski SF, Mulloy B, Morris H, Cremer PS, Dell A, Adang MJ, Aroian RV, 2005. Glycolipids as receptors for Bacillus thuringiensis crystal toxin. Science 307: 922925.
    [Google Scholar]
  35. Griffitts JS, Huffman DL, Whitacre JL, Barrows BD, Marroquin LD, Muller R, Brown JR, Hennet T, Esko JD, Aroian RV, 2003. Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions. J Biol Chem 278: 4559445602.
    [Google Scholar]
  36. Griffitts JS, Whitacre JL, Stevens DE, Aroian RV, 2001. Bt toxin resistance from loss of a putative carbohydrate-modifying enzyme. Science 293: 860864.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.19-0083
Loading
/content/journals/10.4269/ajtmh.19-0083
Loading

Data & Media loading...

  • Received : 27 Jan 2019
  • Accepted : 29 Jul 2019
  • Published online : 16 Sep 2019
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error