_Int. J. Mol. Sci._**2013**, _14_, 16321-16332; doi:10.3390/ijms140816321  
International Journal of  
Molecular Sciences  
ISSN 1422-0067  
www.mdpi.com/journal/ijms  
_Article_  
**The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcus Infection**  
**[PERSON] \({}^{1,\dagger,\ast}\), [PERSON] \({}^{2,\dagger}\), [PERSON] \({}^{3}\), [PERSON] \({}^{4}\), [PERSON] \({}^{2}\), [PERSON] \({}^{4}\), [PERSON] \({}^{5}\), [PERSON] \({}^{2}\), [PERSON] \({}^{5}\), [PERSON] \({}^{3}\), [PERSON] \({}^{4}\), [PERSON] \({}^{2}\) and [PERSON] \({}^{1}\)**  
* Clinic of Dermatology, Department of Clinical and Molecular Sciences, Universit aPolitecnica delle Marche-Ospedali Rianiti, Ancona 60020, Italy; E-Mail: [EMAIL_ADDRESS]
* Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Universit aPolitecnica delle Marche-Ospedali Rianiti, Ancona 60020, Italy; E-Mails: [EMAIL_ADDRESS] (O.C.); [EMAIL_ADDRESS] (C.S.); [EMAIL_ADDRESS] (P.C.); [EMAIL_ADDRESS] (A.G.)
* Centre for Abdominal Surgery and Organ Transplant, Universit aPolitecnica delle Marche-Ospedali Rianiti, Ancona 60020, Italy; E-Mails: [EMAIL_ADDRESS] (F.M.); [EMAIL_ADDRESS] (M.V.)
* Department of Pharmacy, Universit adegli Studi G. D'Annunzio, Chieti-Pescara 66013, Italy; E-Mails: [EMAIL_ADDRESS] (I.C.); [EMAIL_ADDRESS] (L.B.); [EMAIL_ADDRESS] (E.F.)
* Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona 60100, Italy; E-Mails: [EMAIL_ADDRESS] (F.O.); [EMAIL_ADDRESS] (M.P.)
* These authors contributed equally to this work.
* Author to whom correspondence should be addressed; E-Mail: [EMAIL_ADDRESS]; Tel.: +39-071-5963494; Fax: +39-071-5963446.  
_Received: 8 April 2013; in revised form: 1 June 2013 / Accepted: 26 July 2013 / Published: 7 August 2013_  
**Abstract:** We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with \(2\times 10^{7}\)colony-forming units of _Staphylococcus aureus_, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an _in vitro_ binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in _in vitro_ studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 \(\times\) 10\({}^{4}\)\(\pm\) 1.2 \(\times\) 10\({}^{4}\) CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 \(\times\) 10\({}^{4}\)\(\pm\) 2.0 \(\times\) 10\({}^{4}\) CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10\({}^{1}\) CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.  
**Keywords:** lipopeptides; tigecycline; FS8; vascular graft infection; bacterial biofilm