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Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles

Antimicrobial peptides (AMPs) exhibit broad-spectrum antimicrobial activity, and have promise as new therapeutic agents. While the adult North American bullfrog (Rana [Lithobates] catesbeiana) is a prolific source of high-potency AMPs, the aquatic tadpole represents a relatively untapped source for...

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Autores principales: Helbing, Caren C., Hammond, S. Austin, Jackman, Shireen H., Houston, Simon, Warren, René L., Cameron, Caroline E., Birol, Inanç
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365531/
https://www.ncbi.nlm.nih.gov/pubmed/30728430
http://dx.doi.org/10.1038/s41598-018-38442-1
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author Helbing, Caren C.
Hammond, S. Austin
Jackman, Shireen H.
Houston, Simon
Warren, René L.
Cameron, Caroline E.
Birol, Inanç
author_facet Helbing, Caren C.
Hammond, S. Austin
Jackman, Shireen H.
Houston, Simon
Warren, René L.
Cameron, Caroline E.
Birol, Inanç
author_sort Helbing, Caren C.
collection PubMed
description Antimicrobial peptides (AMPs) exhibit broad-spectrum antimicrobial activity, and have promise as new therapeutic agents. While the adult North American bullfrog (Rana [Lithobates] catesbeiana) is a prolific source of high-potency AMPs, the aquatic tadpole represents a relatively untapped source for new AMP discovery. The recent publication of the bullfrog genome and transcriptomic resources provides an opportune bridge between known AMPs and bioinformatics-based AMP discovery. The objective of the present study was to identify novel AMPs with therapeutic potential using a combined bioinformatics and wet lab-based approach. In the present study, we identified seven novel AMP precursor-encoding transcripts expressed in the tadpole. Comparison of their amino acid sequences with known AMPs revealed evidence of mature peptide sequence conservation with variation in the prepro sequence. Two mature peptide sequences were unique and demonstrated bacteriostatic and bactericidal activity against Mycobacteria but not Gram-negative or Gram-positive bacteria. Nine known and seven novel AMP-encoding transcripts were detected in premetamorphic tadpole back skin, olfactory epithelium, liver, and/or tail fin. Treatment of tadpoles with 10 nM 3,5,3′-triiodothyronine for 48 h did not affect transcript abundance in the back skin, and had limited impact on these transcripts in the other three tissues. Gene mapping revealed considerable diversity in size (1.6–15 kbp) and exon number (one to four) of AMP-encoding genes with clear evidence of alternative splicing leading to both prepro and mature amino acid sequence diversity. These findings verify the accuracy and utility of the bullfrog genome assembly, and set a firm foundation for bioinformatics-based AMP discovery.
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spelling pubmed-63655312019-02-08 Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles Helbing, Caren C. Hammond, S. Austin Jackman, Shireen H. Houston, Simon Warren, René L. Cameron, Caroline E. Birol, Inanç Sci Rep Article Antimicrobial peptides (AMPs) exhibit broad-spectrum antimicrobial activity, and have promise as new therapeutic agents. While the adult North American bullfrog (Rana [Lithobates] catesbeiana) is a prolific source of high-potency AMPs, the aquatic tadpole represents a relatively untapped source for new AMP discovery. The recent publication of the bullfrog genome and transcriptomic resources provides an opportune bridge between known AMPs and bioinformatics-based AMP discovery. The objective of the present study was to identify novel AMPs with therapeutic potential using a combined bioinformatics and wet lab-based approach. In the present study, we identified seven novel AMP precursor-encoding transcripts expressed in the tadpole. Comparison of their amino acid sequences with known AMPs revealed evidence of mature peptide sequence conservation with variation in the prepro sequence. Two mature peptide sequences were unique and demonstrated bacteriostatic and bactericidal activity against Mycobacteria but not Gram-negative or Gram-positive bacteria. Nine known and seven novel AMP-encoding transcripts were detected in premetamorphic tadpole back skin, olfactory epithelium, liver, and/or tail fin. Treatment of tadpoles with 10 nM 3,5,3′-triiodothyronine for 48 h did not affect transcript abundance in the back skin, and had limited impact on these transcripts in the other three tissues. Gene mapping revealed considerable diversity in size (1.6–15 kbp) and exon number (one to four) of AMP-encoding genes with clear evidence of alternative splicing leading to both prepro and mature amino acid sequence diversity. These findings verify the accuracy and utility of the bullfrog genome assembly, and set a firm foundation for bioinformatics-based AMP discovery. Nature Publishing Group UK 2019-02-06 /pmc/articles/PMC6365531/ /pubmed/30728430 http://dx.doi.org/10.1038/s41598-018-38442-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Helbing, Caren C.
Hammond, S. Austin
Jackman, Shireen H.
Houston, Simon
Warren, René L.
Cameron, Caroline E.
Birol, Inanç
Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title_full Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title_fullStr Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title_full_unstemmed Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title_short Antimicrobial peptides from Rana [Lithobates] catesbeiana: Gene structure and bioinformatic identification of novel forms from tadpoles
title_sort antimicrobial peptides from rana [lithobates] catesbeiana: gene structure and bioinformatic identification of novel forms from tadpoles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365531/
https://www.ncbi.nlm.nih.gov/pubmed/30728430
http://dx.doi.org/10.1038/s41598-018-38442-1
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