## 1 Introduction  
Healthcare-associated infections (HAIs) are defined as infections not present at the time the patient's healthcare begins, but which arise afterwards [1]. Unfortunately, HAIs are an increasing problem in modern healthcare because they are costly to the health service and to patients and despite current attempts to resolve the problem, HAI still causes significant patient mortality [1].  
_S. aureus_ is also one of the most common pathogens in biofilm related infections of indwelling medical devices [2; 3; 4]. Bacteria can attach to the surface of biomaterials or tissues and form a multilayered structure consisting of bacterial cells enclosed in an extracellular polymeric matrix [5]. Bacterial behavior within biofilms is regulated by the phenomenon of quorum sensing (QS) [6; 7]. Once formed, biofilms may be up to 1000 times more resistant to antimicrobial agents than planktonic cells alone making them particularly difficult to eliminate [8; 9]. Several compounds have been used in many _in vitro_ and _in vivo_ biofilm models [10; 11; 12; 13; 14], but none of them significantly eradicate bacterial colonization. Moreover, the widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains [15; 16]. Tigecycline, a derivate of minocycline, is a glyclycycline that exhibits potent activity against a broad spectrum of bacteria, including staphylococci. Recent reports have shown synergistic effect when tigecycline was combined with other clinically used antibiotics or antimicrobial peptides [17; 18; 19]. A novel strategy to prevent biofilm formation is based on the interference with the bacterial cell-cell communication that leads to the virulence phenotype. It is well known that bacteria communicate their cell density by the production of chemical signals in a process known as quorum sensing [20]. This type of signaling allows the bacteria to coordinate the expression of particular genes necessary for their survival. In the case of staphylococci and e.g., _Pseudomonas aeruginosa_, quorum-sensing systems regulate biofilm architecture and detachment, as well as production of toxins [21, 22, 23].  
_S. aureus_ virulence can be inhibited by the heptapeptide RNA-III inhibiting peptide (RIP, corresponding to the sequence H-Tyr-Ser-Pro-Trp-Thr-Asn-Phe-NH\({}_{2}\)) by interfering with the known function of staphylococcus quorum sensing [24, 25]. RIP is able to inhibit the _in vivo_ formation of staphylococcal biofilm and the agr-regulated toxins production [26]; moreover it shows also synergic effect with most of the common antibiotics used against _S. aureus_ infections [13]. Recently, we started a RIP structure-activity relationship study to identify the contribution of each amino acid to its activity synthesizing a series of single alanine mutants of RIP (data not yet published). Alanine is often selected for such scans because it is assumed that single alanine substitutions do not disrupt the secondary structure of the peptide [27]. Among the seven RIP derivatives synthetized, the quorum-sensing inhibitor FS3 (corresponding to the sequence H-Tyr-Ala-Pro-Trp-Thr-Asn-Phe-NH\({}_{2}\))--obtained substituting the serine residue with alanine in position 2 from the RIP--resulted to enhance the daptomycin efficacy in a rat model of staphylococcal infection [28].  
In the present study, we have investigated the efficacy of tiegecycline and FS8 (a RIP derivative, corresponding to the sequence H-Tyr-Ser-Pro-Trp-Thr-Asn-Ala-NH\({}_{2}\), obtained by substituting the phenylalanine residue with alanine in position 7 from the RIP, (Figure 1) alone or combined in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection.