title: The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing prosthesis biofilm in an animal model of staphylococcal infection.
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 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.
authors: Clinic of Dermatology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche-Ospedali Riuniti, Ancona 60020, Italy. o.simonetti@univpm.it
authors: Oriana
authors: O
authors: Simonetti
authors: Oscar
authors: O
authors: Cirioni
authors: Federico
authors: F
authors: Mocchegiani
authors: Ivana
authors: I
authors: Cacciatore
authors: Carmela
authors: C
authors: Silvestri
authors: Leonardo
authors: L
authors: Baldassarre
authors: Fiorenza
authors: F
authors: Orlando
authors: Pamela
authors: P
authors: Castelli
authors: Mauro
authors: M
authors: Provinciali
authors: Marco
authors: M
authors: Vivarelli
authors: Erika
authors: E
authors: Fornasari
authors: Andrea
authors: A
authors: Giacometti
authors: Annamaria
authors: A
authors: Offidani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011093:Polyethylene Terephthalates / Q000737:chemistry; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D011485:Protein Binding; D053038:Quorum Sensing / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D011093:Polyethylene Terephthalates; C586978:tyrosyl-seryl-prolyl-tryptophyl-threonyl-asparagyl-alaninamide; D000078304:Tigecycline; D008911:Minocycline
references: FEMS Immunol Med Microbiol. 2010 Mar;58(2):147-60
references: 19793317
references: Antimicrob Agents Chemother. 2008 Jun;52(6):2205-11
references: 18391046
references: J Pept Sci. 2012 Sep;18(9):567-78
references: 22807132
references: J Microbiol Methods. 2000 Apr;40(2):175-9
references: 10699673
references: Peptides. 2013 Feb;40:77-81
references: 23262356
references: Science. 1998 Apr 10;280(5361):295-8
references: 9535661
references: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S350-9
references: 18462090
references: FEMS Microbiol Rev. 2004 May;28(2):183-200
references: 15109784
references: J Hosp Infect. 2008 May;69(1):62-8
references: 18395296
references: Trends Microbiol. 1997 May;5(5):184-8
references: 9160506
references: Peptides. 2005 Feb;26(2):169-75
references: 15629527
references: Diagn Microbiol Infect Dis. 2000 Jan;36(1):19-36
references: 10744364
references: Clin Infect Dis. 1998 May;26(5):1182-7
references: 9597250
references: Peptides. 2006 Jun;27(6):1210-6
references: 16289474
references: Mol Microbiol. 2003 Jun;48(6):1429-49
references: 12791129
references: Am Surg. 1998 Jan;64(1):39-45; discussion 45-6
references: 9457036
references: Biotechnol Adv. 2013 Mar-Apr;31(2):224-45
references: 23142623
references: Int J Artif Organs. 2009 Sep;32(9):600-10
references: 19856269
references: Antimicrob Agents Chemother. 2007 Jun;51(6):2226-9
references: 17371825
references: J Clin Microbiol. 1985 Dec;22(6):996-1006
references: 3905855
references: Mol Pharmacol. 2008 May;73(5):1578-86
references: 18314496
references: Cardiovasc Surg. 1996 Jun;4(3):389-92
references: 8782944
references: J Antimicrob Chemother. 2012 Jan;67(1):191-201
references: 22065244
references: J Hosp Infect. 2008 Nov;70 Suppl 2:3-10
references: 19022115
references: J Antimicrob Chemother. 2009 Sep;64 Suppl 1:i29-36
references: 19675016
references: World J Surg. 1998 Feb;22(2):118-26
references: 9451926
references: J Infect Dis. 2006 Jan 15;193(2):180-6
references: 16362881
references: Science. 1999 May 21;284(5418):1318-22
references: 10334980
references: Clin Microbiol Rev. 2002 Apr;15(2):167-93
references: 11932229
references: ChemMedChem. 2012 Nov;7(11):2021-9
references: 22976949
references: Med Res Rev. 2010 Jan;30(1):1-22
references: 19399829
references: Can J Vet Res. 2002 Apr;66(2):86-92
references: 11989739
references: Chem Biol Drug Des. 2013 Jan;81(1):148-65
references: 23253136
references: Int J Antimicrob Agents. 2008 Dec;32 Suppl 4:S215-22
references: 19134522
references: Arch Surg. 1995 Dec;130(12):1345-50
references: 7492284
references: J Antimicrob Chemother. 2003 Oct;52(4):724-6
references: 12951347
references: Peptides. 2001 Oct;22(10):1609-20
references: 11587789