title: Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound.
abstract: 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.
authors.affiliation: Clinic of Dermatology, Department of Clinical and Molecular Sciences; Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Simonetti
authors.affiliation: Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.affiliation: Department of Pharmacy, Università degli Studi G. D'Annunzio, Chieti-Pescara, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.affiliation: Department of Pharmacy, Università degli Studi G. D'Annunzio, Chieti-Pescara, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Baldassarre
authors.affiliation: Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.affiliation: Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pierpaoli
authors.affiliation: Clinic of Dermatology, Department of Clinical and Molecular Sciences; Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.affiliation: Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Orsetti
authors.affiliation: Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.affiliation: Department of Pharmacy, Università degli Studi G. D'Annunzio, Chieti-Pescara, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Fornasari
authors.affiliation: Department of Pharmacy, Università degli Studi G. D'Annunzio, Chieti-Pescara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.affiliation: Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.affiliation: Clinic of Dermatology, Department of Clinical and Molecular Sciences; Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Offidani
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives; D009842:Oligopeptides / Q000008:administration & dosage*; D053038:Quorum Sensing / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000078304:Tigecycline; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; C111711:RNAIII inhibiting peptide; D000078304:Tigecycline; D008911:Minocycline