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A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity
Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hy...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274485/ https://www.ncbi.nlm.nih.gov/pubmed/32453775 http://dx.doi.org/10.1371/journal.ppat.1008600 |
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author | O’Connor, Roberta M. Nepveux V, Felix J. Abenoja, Jaypee Bowden, Gregory Reis, Patricia Beaushaw, Josiah Bone Relat, Rachel M. Driskell, Iwona Gimenez, Fernanda Riggs, Michael W. Schaefer, Deborah A. Schmidt, Eric W. Lin, Zhenjian Distel, Daniel L. Clardy, Jon Ramadhar, Timothy R. Allred, David R. Fritz, Heather M. Rathod, Pradipsinh Chery, Laura White, John |
author_facet | O’Connor, Roberta M. Nepveux V, Felix J. Abenoja, Jaypee Bowden, Gregory Reis, Patricia Beaushaw, Josiah Bone Relat, Rachel M. Driskell, Iwona Gimenez, Fernanda Riggs, Michael W. Schaefer, Deborah A. Schmidt, Eric W. Lin, Zhenjian Distel, Daniel L. Clardy, Jon Ramadhar, Timothy R. Allred, David R. Fritz, Heather M. Rathod, Pradipsinh Chery, Laura White, John |
author_sort | O’Connor, Roberta M. |
collection | PubMed |
description | Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC(50) of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics. |
format | Online Article Text |
id | pubmed-7274485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-72744852020-06-16 A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity O’Connor, Roberta M. Nepveux V, Felix J. Abenoja, Jaypee Bowden, Gregory Reis, Patricia Beaushaw, Josiah Bone Relat, Rachel M. Driskell, Iwona Gimenez, Fernanda Riggs, Michael W. Schaefer, Deborah A. Schmidt, Eric W. Lin, Zhenjian Distel, Daniel L. Clardy, Jon Ramadhar, Timothy R. Allred, David R. Fritz, Heather M. Rathod, Pradipsinh Chery, Laura White, John PLoS Pathog Research Article Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC(50) of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics. Public Library of Science 2020-05-26 /pmc/articles/PMC7274485/ /pubmed/32453775 http://dx.doi.org/10.1371/journal.ppat.1008600 Text en © 2020 O’Connor 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article O’Connor, Roberta M. Nepveux V, Felix J. Abenoja, Jaypee Bowden, Gregory Reis, Patricia Beaushaw, Josiah Bone Relat, Rachel M. Driskell, Iwona Gimenez, Fernanda Riggs, Michael W. Schaefer, Deborah A. Schmidt, Eric W. Lin, Zhenjian Distel, Daniel L. Clardy, Jon Ramadhar, Timothy R. Allred, David R. Fritz, Heather M. Rathod, Pradipsinh Chery, Laura White, John A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title | A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title_full | A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title_fullStr | A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title_full_unstemmed | A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title_short | A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
title_sort | symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274485/ https://www.ncbi.nlm.nih.gov/pubmed/32453775 http://dx.doi.org/10.1371/journal.ppat.1008600 |
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