Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity
The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and m...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458470/ https://www.ncbi.nlm.nih.gov/pubmed/28110506 http://dx.doi.org/10.1002/mbo3.435 |
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author | Davis, Elizabeth Sloan, Tyler Aurelius, Krista Barbour, Angela Bodey, Elijah Clark, Brigette Dennis, Celeste Drown, Rachel Fleming, Megan Humbert, Allison Glasgo, Elizabeth Kerns, Trent Lingro, Kelly McMillin, MacKenzie Meyer, Aaron Pope, Breanna Stalevicz, April Steffen, Brittney Steindl, Austin Williams, Carolyn Wimberley, Carmen Zenas, Robert Butela, Kristen Wildschutte, Hans |
author_facet | Davis, Elizabeth Sloan, Tyler Aurelius, Krista Barbour, Angela Bodey, Elijah Clark, Brigette Dennis, Celeste Drown, Rachel Fleming, Megan Humbert, Allison Glasgo, Elizabeth Kerns, Trent Lingro, Kelly McMillin, MacKenzie Meyer, Aaron Pope, Breanna Stalevicz, April Steffen, Brittney Steindl, Austin Williams, Carolyn Wimberley, Carmen Zenas, Robert Butela, Kristen Wildschutte, Hans |
author_sort | Davis, Elizabeth |
collection | PubMed |
description | The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil‐derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole‐genome sequencing and linker‐mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin‐resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. |
format | Online Article Text |
id | pubmed-5458470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54584702017-06-06 Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity Davis, Elizabeth Sloan, Tyler Aurelius, Krista Barbour, Angela Bodey, Elijah Clark, Brigette Dennis, Celeste Drown, Rachel Fleming, Megan Humbert, Allison Glasgo, Elizabeth Kerns, Trent Lingro, Kelly McMillin, MacKenzie Meyer, Aaron Pope, Breanna Stalevicz, April Steffen, Brittney Steindl, Austin Williams, Carolyn Wimberley, Carmen Zenas, Robert Butela, Kristen Wildschutte, Hans Microbiologyopen Original Research The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil‐derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole‐genome sequencing and linker‐mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin‐resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. John Wiley and Sons Inc. 2017-01-22 /pmc/articles/PMC5458470/ /pubmed/28110506 http://dx.doi.org/10.1002/mbo3.435 Text en © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Davis, Elizabeth Sloan, Tyler Aurelius, Krista Barbour, Angela Bodey, Elijah Clark, Brigette Dennis, Celeste Drown, Rachel Fleming, Megan Humbert, Allison Glasgo, Elizabeth Kerns, Trent Lingro, Kelly McMillin, MacKenzie Meyer, Aaron Pope, Breanna Stalevicz, April Steffen, Brittney Steindl, Austin Williams, Carolyn Wimberley, Carmen Zenas, Robert Butela, Kristen Wildschutte, Hans Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title | Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title_full | Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title_fullStr | Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title_full_unstemmed | Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title_short | Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
title_sort | antibiotic discovery throughout the small world initiative: a molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458470/ https://www.ncbi.nlm.nih.gov/pubmed/28110506 http://dx.doi.org/10.1002/mbo3.435 |
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