The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation.
Gramicidin A is an antimicrobial peptide that destroys gram-positive bacteria. The bactericidal mechanism of antimicrobial peptides has been linked to membrane permeation and metabolism disruption as well as interruption of DNA and protein functions. However, the exact bacterial killing mechanism of...
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doaj-29ff7cbcb4784f919fc83692447085f52021-03-03T20:10:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011706510.1371/journal.pone.0117065The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation.Je-Wen LiouYu-Jiun HungChin-Hao YangYi-Cheng ChenGramicidin A is an antimicrobial peptide that destroys gram-positive bacteria. The bactericidal mechanism of antimicrobial peptides has been linked to membrane permeation and metabolism disruption as well as interruption of DNA and protein functions. However, the exact bacterial killing mechanism of gramicidin A is not clearly understood. In the present study, we examined the antimicrobial activity of gramicidin A on Staphylococcus aureus using biochemical and biophysical methods, including hydroxyl radical and NAD+/NADH cycling assays, atomic force microscopy, and Fourier transform infrared spectroscopy. Gramicidin A induced membrane permeabilization and changed the composition of the membrane. The morphology of Staphylococcus aureus during gramicidin A destruction was divided into four stages: pore formation, water permeability, bacterial flattening, and lysis. Changes in membrane composition included the destruction of membrane lipids, proteins, and carbohydrates. Most interestingly, we demonstrated that gramicidin A not only caused membrane permeabilization but also induced the formation of hydroxyl radicals, which are a possible end product of the transient depletion of NADH from the tricarboxylic acid cycle. The latter may be the main cause of complete Staphylococcus aureus killing. This new finding may provide insight into the underlying bactericidal mechanism of gA.https://doi.org/10.1371/journal.pone.0117065 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Je-Wen Liou Yu-Jiun Hung Chin-Hao Yang Yi-Cheng Chen |
spellingShingle |
Je-Wen Liou Yu-Jiun Hung Chin-Hao Yang Yi-Cheng Chen The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. PLoS ONE |
author_facet |
Je-Wen Liou Yu-Jiun Hung Chin-Hao Yang Yi-Cheng Chen |
author_sort |
Je-Wen Liou |
title |
The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. |
title_short |
The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. |
title_full |
The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. |
title_fullStr |
The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. |
title_full_unstemmed |
The antimicrobial activity of gramicidin A is associated with hydroxyl radical formation. |
title_sort |
antimicrobial activity of gramicidin a is associated with hydroxyl radical formation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Gramicidin A is an antimicrobial peptide that destroys gram-positive bacteria. The bactericidal mechanism of antimicrobial peptides has been linked to membrane permeation and metabolism disruption as well as interruption of DNA and protein functions. However, the exact bacterial killing mechanism of gramicidin A is not clearly understood. In the present study, we examined the antimicrobial activity of gramicidin A on Staphylococcus aureus using biochemical and biophysical methods, including hydroxyl radical and NAD+/NADH cycling assays, atomic force microscopy, and Fourier transform infrared spectroscopy. Gramicidin A induced membrane permeabilization and changed the composition of the membrane. The morphology of Staphylococcus aureus during gramicidin A destruction was divided into four stages: pore formation, water permeability, bacterial flattening, and lysis. Changes in membrane composition included the destruction of membrane lipids, proteins, and carbohydrates. Most interestingly, we demonstrated that gramicidin A not only caused membrane permeabilization but also induced the formation of hydroxyl radicals, which are a possible end product of the transient depletion of NADH from the tricarboxylic acid cycle. The latter may be the main cause of complete Staphylococcus aureus killing. This new finding may provide insight into the underlying bactericidal mechanism of gA. |
url |
https://doi.org/10.1371/journal.pone.0117065 |
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