Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum.
Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the inte...
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ftdoajarticles:oai:doaj.org/article:87b50503691f4c5b92d681d5407bf288 2023-05-15T15:13:40+02:00 Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. Joseph F Urban Yan Hu Melanie M Miller Ulrike Scheib Ying Y Yiu Raffi V Aroian 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002263 https://doaj.org/article/87b50503691f4c5b92d681d5407bf288 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3688533?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002263 https://doaj.org/article/87b50503691f4c5b92d681d5407bf288 PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2263 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002263 2022-12-31T01:58:30Z Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 6 e2263 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Joseph F Urban Yan Hu Melanie M Miller Ulrike Scheib Ying Y Yiu Raffi V Aroian Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract. |
format |
Article in Journal/Newspaper |
author |
Joseph F Urban Yan Hu Melanie M Miller Ulrike Scheib Ying Y Yiu Raffi V Aroian |
author_facet |
Joseph F Urban Yan Hu Melanie M Miller Ulrike Scheib Ying Y Yiu Raffi V Aroian |
author_sort |
Joseph F Urban |
title |
Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
title_short |
Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
title_full |
Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
title_fullStr |
Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
title_full_unstemmed |
Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. |
title_sort |
bacillus thuringiensis-derived cry5b has potent anthelmintic activity against ascaris suum. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002263 https://doaj.org/article/87b50503691f4c5b92d681d5407bf288 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 6, p e2263 (2013) |
op_relation |
http://europepmc.org/articles/PMC3688533?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002263 https://doaj.org/article/87b50503691f4c5b92d681d5407bf288 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002263 |
container_title |
PLoS Neglected Tropical Diseases |
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7 |
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6 |
container_start_page |
e2263 |
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1766344199793278976 |