Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin.
The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a c...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6191125?pdf=render |
| _version_ | 1828194360238276608 |
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| author | Sébastien Cardon Emmanuelle Sachon Ludovic Carlier Thierry Drujon Astrid Walrant Estefanía Alemán-Navarro Verónica Martínez-Osorio Dominique Guianvarc'h Sandrine Sagan Yannick Fleury Rodrigue Marquant Christophe Piesse Yvonne Rosenstein Constance Auvynet Claire Lacombe |
| author_facet | Sébastien Cardon Emmanuelle Sachon Ludovic Carlier Thierry Drujon Astrid Walrant Estefanía Alemán-Navarro Verónica Martínez-Osorio Dominique Guianvarc'h Sandrine Sagan Yannick Fleury Rodrigue Marquant Christophe Piesse Yvonne Rosenstein Constance Auvynet Claire Lacombe |
| author_sort | Sébastien Cardon |
| collection | DOAJ |
| description | The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an α-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan. |
| first_indexed | 2024-04-12T09:23:38Z |
| format | Article |
| id | doaj.art-78b544e90a0947459e588490d3adcb67 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T09:23:38Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-78b544e90a0947459e588490d3adcb672022-12-22T03:38:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020572710.1371/journal.pone.0205727Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin.Sébastien CardonEmmanuelle SachonLudovic CarlierThierry DrujonAstrid WalrantEstefanía Alemán-NavarroVerónica Martínez-OsorioDominique Guianvarc'hSandrine SaganYannick FleuryRodrigue MarquantChristophe PiesseYvonne RosensteinConstance AuvynetClaire LacombeThe occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an α-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan.http://europepmc.org/articles/PMC6191125?pdf=render |
| spellingShingle | Sébastien Cardon Emmanuelle Sachon Ludovic Carlier Thierry Drujon Astrid Walrant Estefanía Alemán-Navarro Verónica Martínez-Osorio Dominique Guianvarc'h Sandrine Sagan Yannick Fleury Rodrigue Marquant Christophe Piesse Yvonne Rosenstein Constance Auvynet Claire Lacombe Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. PLoS ONE |
| title | Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. |
| title_full | Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. |
| title_fullStr | Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. |
| title_full_unstemmed | Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. |
| title_short | Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin. |
| title_sort | peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of dms da6 a gram positive selective antimicrobial peptide isolated from pachymedusa dacnicolor skin |
| url | http://europepmc.org/articles/PMC6191125?pdf=render |
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