A number of genes have been reported to be involved in these steps of biofilm formation. Some of these genes were selected for evaluation of their susceptibility to gene expression inhibition by CCG-203592 using a real time RTPCR approach. The genes down-regulated or up-regulated by CCG-203592 are involved in biofilm VE-822 formation at different stages of biofilm formation. The icaADBC operon encodes enzymes involved in biosynthesis of polysaccharide intercellular adhesin or polymeric N-acetyl-glucosamine that plays important roles in biofilm formation. Deletion of the ica locus significantly decreased S. aureus biofilm formation. Downregulation of icaA could decrease production of PIA/PNAG, leading to reduction of biofilm formation. Interestingly, icaA was up-regulated during ML phase, but down-regulated at 
S phase. The net outcome of the effect of CCG-203592 on icaA could result from the combined effect of the dynamic changes of gene expression. The dltABCD operon encodes four proteins responsible for esterification of teichoic acids with D-alanine. Deficiency in dltA results in a stronger negative net charge on the CP-358774 citations bacterial cell surface and defects in the initial binding of bacteria to the surface in biofilm formation. Down-regulation of dltD in the same operon could have similar effects. Autolysin altA is a major peptidoglycan hydrolase that cleaves newly synthesized peptidoglycan components before they are incorporated into the cell wall. Primary attachment of bacteria to surfaces is impaired in altA null mutants. SPA gene was consistently down-regulated by CCG-203592 in all three phases tested. SPA is able to induce cell aggregation and biofilm formation. sdrD is one of the microbial surface components recognizing adhesive matrix molecules that play important roles in mediating bacteria adhesion to host tissues and forming biofilm though the exact function of sdrD is unkown. sspB encodes a cysteine protease that is regulated by agr system. Inactivating sspC which is an inhibitor of sspB, enhances the attachment of bacteria to solid surfaces and biofilm formation, suggesting that sspB has positive effects on biofilm formation. SigB is an alternative sigma factor that regulates a large regulon and inactivating SigB decreases biofilm formation by S. aureus and increases RNAIII level. RNAIII is a component of the agr quorum-sensing system which regulates gene expression in response to outside signals. Inhibition of agr system is important for biofilm development and agr also mediates biofilm dispersal. The influence of agr system on biofilm development is multifaceted and complicated, depending on experimental conditions. Hla was shown to be required for S. aureus biofilm formation and deficiency in Hla caused defects in biofilm formation. Taken together, down-regulating the above genes could negatively impact biofilm formation. On the other hand, psma operon encodes four short PSMa peptides. Deletion of psma causes defects in formation of biofilm channels and biofilm detachment and regrowth which suggested that PSMs are important for biofilm maturation and detachment. Lack of PSMs led to increased biofilm volume and thickness. The lrg operon is responsible for inhibition of murein hydrolase activity of the CidA protein. Mutant inactivating LrgAB operon exhibits increased biofilm adherence and matrix-associated eDNA, and forms biofilm with reduced biomass and defective structures compared.