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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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.
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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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