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Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice

BACKGROUND: Intestinal parasitic nematode diseases are one of the great diseases of our time. Intestinal roundworm parasites, including hookworms, whipworms, and Ascaris, infect well over 1 billion people and cause significant morbidity, especially in children and pregnant women. To date, there is o...

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Detalles Bibliográficos
Autores principales: Hu, Yan, Georghiou, Sophia B., Kelleher, Alan J., Aroian, Raffi V.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830470/
https://www.ncbi.nlm.nih.gov/pubmed/20209154
http://dx.doi.org/10.1371/journal.pntd.0000614
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author Hu, Yan
Georghiou, Sophia B.
Kelleher, Alan J.
Aroian, Raffi V.
author_facet Hu, Yan
Georghiou, Sophia B.
Kelleher, Alan J.
Aroian, Raffi V.
author_sort Hu, Yan
collection PubMed
description BACKGROUND: Intestinal parasitic nematode diseases are one of the great diseases of our time. Intestinal roundworm parasites, including hookworms, whipworms, and Ascaris, infect well over 1 billion people and cause significant morbidity, especially in children and pregnant women. To date, there is only one drug, albendazole, with adequate efficacy against these parasites to be used in mass drug administration, although tribendimidine may emerge as a second. Given the hundreds of millions of people to be treated, the threat of parasite resistance, and the inadequacy of current treatments, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal (Cry) proteins are the most common used biologically produced insecticides in the world and are considered non-toxic to vertebrates. METHODS/PRINCIPAL FINDINGS: Here we study the ability of a nematicidal Cry protein, Cry5B, to effect a cure in mice of a chronic roundworm infection caused by the natural intestinal parasite, Heligmosomoides bakeri (formerly polygyrus). We show that Cry5B produced from either of two Bt strains can act as an anthelmintic in vivo when administered as a single dose, achieving a ∼98% reduction in parasite egg production and ∼70% reduction in worm burdens when delivered per os at ∼700 nmoles/kg (90–100 mg/kg). Furthermore, our data, combined with the findings of others, suggest that the relative efficacy of Cry5B is either comparable or superior to current anthelmintics. We also demonstrate that Cry5B is likely to be degraded quite rapidly in the stomach, suggesting that the actual dose reaching the parasites is very small. CONCLUSIONS/SIGNIFICANCE: This study indicates that Bt Cry proteins such as Cry5B have excellent anthelmintic properties in vivo and that proper formulation of the protein is likely to reveal a superior anthelmintic.
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spelling pubmed-28304702010-03-05 Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice Hu, Yan Georghiou, Sophia B. Kelleher, Alan J. Aroian, Raffi V. PLoS Negl Trop Dis Research Article BACKGROUND: Intestinal parasitic nematode diseases are one of the great diseases of our time. Intestinal roundworm parasites, including hookworms, whipworms, and Ascaris, infect well over 1 billion people and cause significant morbidity, especially in children and pregnant women. To date, there is only one drug, albendazole, with adequate efficacy against these parasites to be used in mass drug administration, although tribendimidine may emerge as a second. Given the hundreds of millions of people to be treated, the threat of parasite resistance, and the inadequacy of current treatments, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal (Cry) proteins are the most common used biologically produced insecticides in the world and are considered non-toxic to vertebrates. METHODS/PRINCIPAL FINDINGS: Here we study the ability of a nematicidal Cry protein, Cry5B, to effect a cure in mice of a chronic roundworm infection caused by the natural intestinal parasite, Heligmosomoides bakeri (formerly polygyrus). We show that Cry5B produced from either of two Bt strains can act as an anthelmintic in vivo when administered as a single dose, achieving a ∼98% reduction in parasite egg production and ∼70% reduction in worm burdens when delivered per os at ∼700 nmoles/kg (90–100 mg/kg). Furthermore, our data, combined with the findings of others, suggest that the relative efficacy of Cry5B is either comparable or superior to current anthelmintics. We also demonstrate that Cry5B is likely to be degraded quite rapidly in the stomach, suggesting that the actual dose reaching the parasites is very small. CONCLUSIONS/SIGNIFICANCE: This study indicates that Bt Cry proteins such as Cry5B have excellent anthelmintic properties in vivo and that proper formulation of the protein is likely to reveal a superior anthelmintic. Public Library of Science 2010-03-02 /pmc/articles/PMC2830470/ /pubmed/20209154 http://dx.doi.org/10.1371/journal.pntd.0000614 Text en Hu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hu, Yan
Georghiou, Sophia B.
Kelleher, Alan J.
Aroian, Raffi V.
Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title_full Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title_fullStr Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title_full_unstemmed Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title_short Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice
title_sort bacillus thuringiensis cry5b protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2830470/
https://www.ncbi.nlm.nih.gov/pubmed/20209154
http://dx.doi.org/10.1371/journal.pntd.0000614
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