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 PF-915275 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 KIN1408 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 to mature wild-type biofilm. Interestingly, CidA was up-regulated during ML and LL phases which could generate similar phenotype as down-regulating lrg. However, mutations in both lrg and CidA caused aberrant biofilm maturation, suggesting that imbalance in their gene expression could disrupt biofilm development. These effects of CCG-203592 may increase biofilm formation, which could be outweighed by the effects of down-regulation of other genes by CCG-203592. As a result, the combined effect of all the affected genes by CCG-203592 may produce net decrease of biofilm formation.
