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The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity

Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have...

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Autores principales: Heulot, Mathieu, Jacquier, Nicolas, Aeby, Sébastien, Le Roy, Didier, Roger, Thierry, Trofimenko, Evgeniya, Barras, David, Greub, Gilbert, Widmann, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461357/
https://www.ncbi.nlm.nih.gov/pubmed/28638371
http://dx.doi.org/10.3389/fmicb.2017.00994
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author Heulot, Mathieu
Jacquier, Nicolas
Aeby, Sébastien
Le Roy, Didier
Roger, Thierry
Trofimenko, Evgeniya
Barras, David
Greub, Gilbert
Widmann, Christian
author_facet Heulot, Mathieu
Jacquier, Nicolas
Aeby, Sébastien
Le Roy, Didier
Roger, Thierry
Trofimenko, Evgeniya
Barras, David
Greub, Gilbert
Widmann, Christian
author_sort Heulot, Mathieu
collection PubMed
description Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP(317−326), induces cancer cell death, inhibits metastatic progression, and sensitizes tumor cells to various anti-cancer treatments in vitro and in vivo. We here report that TAT-RasGAP(317−326) also possesses antimicrobial activity. In vitro, TAT-RasGAP(317−326), but not mutated or truncated forms of the peptide, efficiently killed a series of bacteria including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa. In vivo experiments revealed that TAT-RasGAP(317−326) protects mice from lethal E. coli-induced peritonitis if administrated locally at the onset of infection. However, the protective effect was lost when treatment was delayed, likely due to rapid clearance and inadequate biodistribution of the peptide. Peptide modifications might overcome these shortcomings to increase the in vivo efficacy of the compound in the context of the currently limited antimicrobial options.
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spelling pubmed-54613572017-06-21 The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity Heulot, Mathieu Jacquier, Nicolas Aeby, Sébastien Le Roy, Didier Roger, Thierry Trofimenko, Evgeniya Barras, David Greub, Gilbert Widmann, Christian Front Microbiol Microbiology Antibiotic resistance has become a major health issue. Nosocomial infections and the prevalence of resistant pathogenic bacterial strains are rising steadily. Therefore, there is an urgent need to develop new classes of antibiotics effective on multi-resistant nosocomial pathogenic bacteria. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP(317−326), induces cancer cell death, inhibits metastatic progression, and sensitizes tumor cells to various anti-cancer treatments in vitro and in vivo. We here report that TAT-RasGAP(317−326) also possesses antimicrobial activity. In vitro, TAT-RasGAP(317−326), but not mutated or truncated forms of the peptide, efficiently killed a series of bacteria including Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa. In vivo experiments revealed that TAT-RasGAP(317−326) protects mice from lethal E. coli-induced peritonitis if administrated locally at the onset of infection. However, the protective effect was lost when treatment was delayed, likely due to rapid clearance and inadequate biodistribution of the peptide. Peptide modifications might overcome these shortcomings to increase the in vivo efficacy of the compound in the context of the currently limited antimicrobial options. Frontiers Media S.A. 2017-06-07 /pmc/articles/PMC5461357/ /pubmed/28638371 http://dx.doi.org/10.3389/fmicb.2017.00994 Text en Copyright © 2017 Heulot, Jacquier, Aeby, Le Roy, Roger, Trofimenko, Barras, Greub and Widmann. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Heulot, Mathieu
Jacquier, Nicolas
Aeby, Sébastien
Le Roy, Didier
Roger, Thierry
Trofimenko, Evgeniya
Barras, David
Greub, Gilbert
Widmann, Christian
The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title_full The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title_fullStr The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title_full_unstemmed The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title_short The Anticancer Peptide TAT-RasGAP(317−326) Exerts Broad Antimicrobial Activity
title_sort anticancer peptide tat-rasgap(317−326) exerts broad antimicrobial activity
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461357/
https://www.ncbi.nlm.nih.gov/pubmed/28638371
http://dx.doi.org/10.3389/fmicb.2017.00994
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