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Bacillus thuringiensis Cry5B is Active against Strongyloides stercoralis in vitro
Strongyloidiasis, caused by Strongyloides stercoralis 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 Bacillus thuringiensis crystal protein Cry5B. Cry5B is highly potent against parasitic nematodes, for example, hookworms and Ascaris suum. Here, we investigated the potential of Cry5B against S. stercoralis. Multiple stages of S. stercoralis, 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.
Author Notes
Financial support: This research was financially supported by the 100th Anniversary Chulalongkorn University for Doctoral Scholarship and by National Institutes of Health National Institute of Allergy and Infectious Diseases (R. V. A., grant number R01 AI056189; J. B. L., grant number R01 AI022662) and Agriculture and Food Research Initiative competitive grant (no. 2015-11323) to R. V. A. from the USDA National Institute of Food and Agriculture.
Authors’ addresses: Sarit Charuchaibovorn, Siriraj Center of Excellence for Stem Cell Research (SiSCR), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, E-mail: sarit.src@gmail.com. Vivornpun Sanprasert and Surang Nuchprayoon, Department of Parasitology, Lymphatic Filariasis and Tropical Medicine Research Unit, Chulalongkorn Medical Research Center (Chula MRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, E-mails: vivornpun@chula.md and fmedstt@gmail.com. Nataya Sutthanont, Lymphatic Filariasis and Tropical Medicine Research Unit, Chulalongkorn Medical Research Center (Chula MRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, E-mail: nanzzy0704@gmail.com. Yan Hu, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, and Biology Department, Worcester State University, Worcester, MA, E-mail: yhu@worcester.edu. Ambily Abraham, Gary R. Ostroff, and Raffi V. Aroian, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, E-mails: ambily.abraham@umassmed.edu, gary.ostroff@umassmed.edu, and raffi.aroian@umassmed.edu. Tegegn G. Jaleta and James B. Lok, Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, E-mails: tjaleta@vet.upenn.edu and jlok@vet.upenn.edu.
These authors contributed equally to this work.