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Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound

In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel R...

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Autores principales: Simonetti, Oriana, Cirioni, Oscar, Cacciatore, Ivana, Baldassarre, Leonardo, Orlando, Fiorenza, Pierpaoli, Elisa, Lucarini, Guendalina, Orsetti, Elena, Provinciali, Mauro, Fornasari, Erika, Di Stefano, Antonio, Giacometti, Andrea, Offidani, Annamaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890846/
https://www.ncbi.nlm.nih.gov/pubmed/27253706
http://dx.doi.org/10.1371/journal.pone.0151956
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author Simonetti, Oriana
Cirioni, Oscar
Cacciatore, Ivana
Baldassarre, Leonardo
Orlando, Fiorenza
Pierpaoli, Elisa
Lucarini, Guendalina
Orsetti, Elena
Provinciali, Mauro
Fornasari, Erika
Di Stefano, Antonio
Giacometti, Andrea
Offidani, Annamaria
author_facet Simonetti, Oriana
Cirioni, Oscar
Cacciatore, Ivana
Baldassarre, Leonardo
Orlando, Fiorenza
Pierpaoli, Elisa
Lucarini, Guendalina
Orsetti, Elena
Provinciali, Mauro
Fornasari, Erika
Di Stefano, Antonio
Giacometti, Andrea
Offidani, Annamaria
author_sort Simonetti, Oriana
collection PubMed
description In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x10(7) CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 10(7) CFU/ml to about 10(3) CFU/g for MSSA and to about 10(4) CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.
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spelling pubmed-48908462016-06-10 Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound Simonetti, Oriana Cirioni, Oscar Cacciatore, Ivana Baldassarre, Leonardo Orlando, Fiorenza Pierpaoli, Elisa Lucarini, Guendalina Orsetti, Elena Provinciali, Mauro Fornasari, Erika Di Stefano, Antonio Giacometti, Andrea Offidani, Annamaria PLoS One Research Article In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x10(7) CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 10(7) CFU/ml to about 10(3) CFU/g for MSSA and to about 10(4) CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models. Public Library of Science 2016-06-02 /pmc/articles/PMC4890846/ /pubmed/27253706 http://dx.doi.org/10.1371/journal.pone.0151956 Text en © 2016 Simonetti et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Simonetti, Oriana
Cirioni, Oscar
Cacciatore, Ivana
Baldassarre, Leonardo
Orlando, Fiorenza
Pierpaoli, Elisa
Lucarini, Guendalina
Orsetti, Elena
Provinciali, Mauro
Fornasari, Erika
Di Stefano, Antonio
Giacometti, Andrea
Offidani, Annamaria
Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title_full Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title_fullStr Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title_full_unstemmed Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title_short Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound
title_sort efficacy of the quorum sensing inhibitor fs10 alone and in combination with tigecycline in an animal model of staphylococcal infected wound
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890846/
https://www.ncbi.nlm.nih.gov/pubmed/27253706
http://dx.doi.org/10.1371/journal.pone.0151956
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