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Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD)
American oyster defensin (AOD) was previously purified from acidified gill extract of the American oyster, Crassostrea virginica. AOD is composed of 38 amino acids with three disulfide bonds and exhibits strong antimicrobial activity against Gram-positive bacteria as well as significant activity aga...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400246/ https://www.ncbi.nlm.nih.gov/pubmed/34436290 http://dx.doi.org/10.3390/md19080451 |
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author | Seo, Jung-Kil Kim, Dong-Gyun Lee, Ji-Eun Park, Kwon-Sam Lee, In-Ah Lee, Ki-Young Kim, Young-Ok Nam, Bo-Hye |
author_facet | Seo, Jung-Kil Kim, Dong-Gyun Lee, Ji-Eun Park, Kwon-Sam Lee, In-Ah Lee, Ki-Young Kim, Young-Ok Nam, Bo-Hye |
author_sort | Seo, Jung-Kil |
collection | PubMed |
description | American oyster defensin (AOD) was previously purified from acidified gill extract of the American oyster, Crassostrea virginica. AOD is composed of 38 amino acids with three disulfide bonds and exhibits strong antimicrobial activity against Gram-positive bacteria as well as significant activity against Gram-negative bacteria. Here, to develop promising peptides into antibiotic candidates, we designed five arginine-rich analogs (A0, A1, A2, A3, and A4), predicted their loop and extended strand/random structures—including nine amino acids and a disulfide bond derived from the C-terminus of AOD—and described their antimicrobial and cytotoxic effects, as well as their modes of action. In our experimental results, the A3 and A4 analogs exhibited potent antimicrobial activity against all test organisms—including four Gram-positive bacteria, six Gram-negative bacteria, and Candida albicans—without cell toxicity. A sequence of experiments, including a membrane permeabilization assay, DNA binding study, and DNA polymerization inhibition test, indicated that the two analogs (A3 and A4) possibly did not act directly on the bacterial membrane but instead interacted with intracellular components such as DNA or DNA amplification reactions. AOD analogs also showed strong bacterial inhibition activity in the plasma environment. In addition, analog-treated microbial cells clearly exhibited membrane disruption, damage, and leakage of cytoplasmic contents. Collectively, our results suggest that two analogs, A3 and A4, have potent antimicrobial activity via DNA interaction and have the potential for development into novel antimicrobial agents. |
format | Online Article Text |
id | pubmed-8400246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84002462021-08-29 Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) Seo, Jung-Kil Kim, Dong-Gyun Lee, Ji-Eun Park, Kwon-Sam Lee, In-Ah Lee, Ki-Young Kim, Young-Ok Nam, Bo-Hye Mar Drugs Article American oyster defensin (AOD) was previously purified from acidified gill extract of the American oyster, Crassostrea virginica. AOD is composed of 38 amino acids with three disulfide bonds and exhibits strong antimicrobial activity against Gram-positive bacteria as well as significant activity against Gram-negative bacteria. Here, to develop promising peptides into antibiotic candidates, we designed five arginine-rich analogs (A0, A1, A2, A3, and A4), predicted their loop and extended strand/random structures—including nine amino acids and a disulfide bond derived from the C-terminus of AOD—and described their antimicrobial and cytotoxic effects, as well as their modes of action. In our experimental results, the A3 and A4 analogs exhibited potent antimicrobial activity against all test organisms—including four Gram-positive bacteria, six Gram-negative bacteria, and Candida albicans—without cell toxicity. A sequence of experiments, including a membrane permeabilization assay, DNA binding study, and DNA polymerization inhibition test, indicated that the two analogs (A3 and A4) possibly did not act directly on the bacterial membrane but instead interacted with intracellular components such as DNA or DNA amplification reactions. AOD analogs also showed strong bacterial inhibition activity in the plasma environment. In addition, analog-treated microbial cells clearly exhibited membrane disruption, damage, and leakage of cytoplasmic contents. Collectively, our results suggest that two analogs, A3 and A4, have potent antimicrobial activity via DNA interaction and have the potential for development into novel antimicrobial agents. MDPI 2021-08-06 /pmc/articles/PMC8400246/ /pubmed/34436290 http://dx.doi.org/10.3390/md19080451 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seo, Jung-Kil Kim, Dong-Gyun Lee, Ji-Eun Park, Kwon-Sam Lee, In-Ah Lee, Ki-Young Kim, Young-Ok Nam, Bo-Hye Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title | Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title_full | Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title_fullStr | Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title_full_unstemmed | Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title_short | Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD) |
title_sort | antimicrobial activity and action mechanisms of arg-rich short analog peptides designed from the c-terminal loop region of american oyster defensin (aod) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400246/ https://www.ncbi.nlm.nih.gov/pubmed/34436290 http://dx.doi.org/10.3390/md19080451 |
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