Thus, infections caused by S. epidermidis biofilms are particularly hard to eradicate. Biofilm formation by S. epidermidis is a multistep process and involves (1) attachment of the bacterial cells to a polymer surface or to the host-derived matrix that has previously coated the polymeric device and (2) accumulation to form multilayered cell clusters with cell-to-cell

adherence mediated by the production of a slimy extracellular matrix (Vadyvaloo & Otto, 2005). Several genes have been identified to play important roles in the biofilm formation of S. epidermidis (Mack et al., 2007). The atlE gene encodes autolysin AtlE, which mediates the initial attachment of S. epidermidis to a polymer surface (Heilmann et al., 1997), and the ica gene locus (icaADBC) encodes the biosynthesis

of polysaccharide intercellular adhesion (PIA), which is essential in the accumulation process (Heilmann et al., 1996). A few regulatory PLX4032 solubility dmso genes of biofilm formation were also identified (Mack et al., 2007). For example, the icaR gene affects the ability of biofilm formation by repressing the icaADBC operon (Conlon et al., 2002). The sarA gene encodes an activator of the icaADBC operon and positively regulates the biofilm formation of S. epidermidis (Tormo et al., 2005). The rsbU gene, a positive regulator of the alternative sigma factor, σB, positively regulates the biofilm formation of S. epidermidis by repressing icaR (Knobloch

et al., buy Fulvestrant 2004). Besides, LuxS (Xu et al., 2006) and Agr (Kong et al., 2006), a quorum-sensing system, also mediate biofilm formation in S. epidermidis. Recent work indicates that the regulation of biofilm formation in S. epidermidis is a complex networking and may involve mechanisms other than the ica system. The sarZ gene encodes a regulator that activates the transcription of the icaADBC operon in an icaR-independent manner and positively regulates the biofilm formation of S. epidermidis (Wang et al., 2008) Additionally, it is not uncommon to find clinical isolates that accumulate biofilm in an ica-independent mode (Ruzicka et al., 2004; Hennig et al., 2007; Qin et al., 2007), which indicates that there may be other mechanisms mediating biofilm formation. Protein degradation is essential for cell viability and homeostasis, and this process is commonly Thymidylate synthase mediated by ATP-dependent proteases. One notable case is ClpXP proteases, which function in degrading SsrA-tagged misfolded proteins (Gottesman et al., 1998), controlling the RpoS concentration in Escherichia coli (Gottesman et al., 1998) and regulating bacterial adaptation to stress (Porankiewicz et al., 1999). ClpXP proteases also play a crucial role in the biofilm formation of Pseudomonas fluorescens (O’Toole & Kolter, 1998), Streptococcus mutans (Lemos & Burne, 2002), Staphylococcus aureus (Frees et al., 2004) and S. epidermidis (Wang et al., 2007).