The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection
1
Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche–Ospedali Riuniti, Ancona 60020, Italy
2
Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche–Ospedali Riuniti, Ancona 60020, Italy
3
Centre for Abdominal Surgery and Organ Transplant, Università Politecnica delle Marche–Ospedali Riuniti, Ancona 60020, Italy
4
Department of Pharmacy, Università degli Studi G. D'Annunzio, Chieti-Pescara 66013, Italy
5
Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona 60100, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2013, 14(8), 16321-16332; https://doi.org/10.3390/ijms140816321
Received: 8 April 2013 / Revised: 1 June 2013 / Accepted: 26 July 2013 / Published: 7 August 2013
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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 x 107 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 x 104 ± 1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 x 104 ± 2.0 x 104 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 101 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