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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Main Authors: Oriana Simonetti, Oscar Cirioni, Ivana Cacciatore, Leonardo Baldassarre, Fiorenza Orlando, Elisa Pierpaoli, Guendalina Lucarini, Elena Orsetti, Mauro Provinciali, Erika Fornasari, Antonio Di Stefano, Andrea Giacometti, Annamaria Offidani
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4890846?pdf=render
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author Oriana Simonetti
Oscar Cirioni
Ivana Cacciatore
Leonardo Baldassarre
Fiorenza Orlando
Elisa Pierpaoli
Guendalina Lucarini
Elena Orsetti
Mauro Provinciali
Erika Fornasari
Antonio Di Stefano
Andrea Giacometti
Annamaria Offidani
author_facet Oriana Simonetti
Oscar Cirioni
Ivana Cacciatore
Leonardo Baldassarre
Fiorenza Orlando
Elisa Pierpaoli
Guendalina Lucarini
Elena Orsetti
Mauro Provinciali
Erika Fornasari
Antonio Di Stefano
Andrea Giacometti
Annamaria Offidani
author_sort Oriana Simonetti
collection DOAJ
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 5x107 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 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 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 doaj.art-1e102437b55c4c7a82f99ff11eb6bd602022-12-22T01:58:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015195610.1371/journal.pone.0151956Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound.Oriana SimonettiOscar CirioniIvana CacciatoreLeonardo BaldassarreFiorenza OrlandoElisa PierpaoliGuendalina LucariniElena OrsettiMauro ProvincialiErika FornasariAntonio Di StefanoAndrea GiacomettiAnnamaria OffidaniIn 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 5x107 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 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 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.http://europepmc.org/articles/PMC4890846?pdf=render
spellingShingle Oriana Simonetti
Oscar Cirioni
Ivana Cacciatore
Leonardo Baldassarre
Fiorenza Orlando
Elisa Pierpaoli
Guendalina Lucarini
Elena Orsetti
Mauro Provinciali
Erika Fornasari
Antonio Di Stefano
Andrea Giacometti
Annamaria Offidani
Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound.
PLoS ONE
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
url http://europepmc.org/articles/PMC4890846?pdf=render
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