PMID- 27253706 OWN - NLM STAT- MEDLINE DCOM- 20170712 LR - 20190213 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 6 DP - 2016 TI - Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound. PG - e0151956 LID - 10.1371/journal.pone.0151956 [doi] LID - e0151956 AB - 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 mug FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 mug 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. FAU - Simonetti, Oriana AU - Simonetti O AD - Clinic of Dermatology, Department of Clinical and Molecular Sciences; Universita Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. FAU - Cirioni, Oscar AU - Cirioni O AD - Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Universita Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. FAU - Cacciatore, Ivana AU - Cacciatore I AD - Department of Pharmacy, Universita degli Studi G. D'Annunzio, Chieti-Pescara, Italy. FAU - Baldassarre, Leonardo AU - Baldassarre L AD - Department of Pharmacy, Universita degli Studi G. D'Annunzio, Chieti-Pescara, Italy. FAU - Orlando, Fiorenza AU - Orlando F AD - Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy. FAU - Pierpaoli, Elisa AU - Pierpaoli E AD - Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy. FAU - Lucarini, Guendalina AU - Lucarini G AD - Clinic of Dermatology, Department of Clinical and Molecular Sciences; Universita Politecnica delle Marche, Ancona, Italy. FAU - Orsetti, Elena AU - Orsetti E AD - Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Universita Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. FAU - Provinciali, Mauro AU - Provinciali M AD - Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy. FAU - Fornasari, Erika AU - Fornasari E AD - Department of Pharmacy, Universita degli Studi G. D'Annunzio, Chieti-Pescara, Italy. FAU - Di Stefano, Antonio AU - Di Stefano A AD - Department of Pharmacy, Universita degli Studi G. D'Annunzio, Chieti-Pescara, Italy. FAU - Giacometti, Andrea AU - Giacometti A AD - Clinic of Infectious Diseases, Italy, Department of Biomedical Sciences and Public Health; Universita Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. FAU - Offidani, Annamaria AU - Offidani A AD - Clinic of Dermatology, Department of Clinical and Molecular Sciences; Universita Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. LA - eng PT - Journal Article DEP - 20160602 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-Bacterial Agents) RN - 0 (Oligopeptides) RN - 0 (RNAIII inhibiting peptide) RN - 70JE2N95KR (Tigecycline) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Anti-Bacterial Agents/administration & dosage MH - Disease Models, Animal MH - Humans MH - Methicillin-Resistant Staphylococcus aureus/*drug effects/pathogenicity MH - Mice MH - Minocycline/administration & dosage/analogs & derivatives MH - Oligopeptides/*administration & dosage MH - Quorum Sensing/drug effects MH - Staphylococcal Infections/*drug therapy/microbiology MH - Tigecycline MH - Wound Infection/*drug therapy/microbiology PMC - PMC4890846 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/06/03 06:00 MHDA- 2017/07/14 06:00 PMCR- 2016/06/02 CRDT- 2016/06/03 06:00 PHST- 2015/09/25 00:00 [received] PHST- 2016/03/06 00:00 [accepted] PHST- 2016/06/03 06:00 [entrez] PHST- 2016/06/03 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2016/06/02 00:00 [pmc-release] AID - PONE-D-15-42378 [pii] AID - 10.1371/journal.pone.0151956 [doi] PST - epublish SO - PLoS One. 2016 Jun 2;11(6):e0151956. doi: 10.1371/journal.pone.0151956. eCollection 2016.