Background and Aim:Staphylococcus aureus is responsible for fatal diseases as a result of the expression of multiple virulence factors, and this organism is one of the most important biofilm-forming pathogens that cause complications ranging infections. Biofilms can be defined as structured aggregation of surface-attached microorganisms kept by an extracellular matrix. Increased resistances of bacteria to antimicrobial agent occur due to dormant phenotype in biofilm phase. The challenge in treating biofilm-associated infections caused by S. aureus is one of the most problems in veterinary and medicine science. Quorum-sensing is based on the synthesis and secretion of small hormone-like molecules (autoinducers). These molecules can bind to cognate receptors and contribute to biofilm formation. The purpose of this article is introducing quorum-sensing inhibitors (QSI) as novel strategies to control biofilm formation by S. aureus. Methods:Two phenotypic tests, including growth on microtitre plates and Congo red agar are used for detection of biofilm formation. Results:QSI consist of synthetic and natural agents. Hammelitannin (HAM) is a non-peptideanalog of the quorum-sensing inhibitor RNAIII-inhibitingpeptide (RIP). HAM decreases both in vitro and in vivo S. aureus attachment. Polymethylmethacrylate(PMMA) was shown to be able to prevent biofilm formation in orthopedic infections caused by methicillin-resistant S. aureus. Poly-trimethylene carbonate (PTMC) is able to inhibit biofilm formation of S. aureus intreatment of osteomyelitis. Antibody against quorum-sensing peptide AP4 is one of the best candidate to suppress S. aureus pathogenicity in mouse abscess infection model. Silver nanoparticles have been shown to enhance quorum-quenching activity and prevention of biofilm formation. Conclusion: A mechanism of action of QSI is repression of signal generation, blockage of signal receptors, and disruption of QS signals. As for the importance of these molecules in the inh
