Moreover, we observed upregulation of sae in the agr mutant and upregulation

of agr in the sae mutant compared with the isogenic Newman strain, suggesting that the Agr and Sae may be inhibiting each other. The SigB mutation did not affect ssl5 and ssl8 expression, but they were downregulated in the agr/sigB double mutant, indicating that SigB probably acts synergistically with Agr in their upregulation. Staphylococcus aureus is a significant human pathogen capable of causing a variety of diseases ranging from mild skin and soft tissue infections to bacteremia, pneumonia, endocarditis, and osteomyelitis Trametinib molecular weight (Lowy, 1998). The ability of S. aureus to cause a wide range of infections is partly due to the expression of a wide array of virulence factors including, but not limited to, cell wall-associated adhesions, clumping factors, exotoxins, and secreted proteins such as staphylococcal superantigen-like (SSL) proteins (Lowy, 1998; Dinges et al., 2000; Williams et al., 2000; Fitzgerald et al., 2003). The SSL proteins are encoded by a cluster of 11 ssl genes located on S. aureus pathogenicity island-2 (Fitzgerald et al., 2003). These proteins have limited sequence homology to the enterotoxins and toxic shock syndrome toxin 1 and thus represent

a novel family of exotoxin-like this website proteins (Williams et al., 2000). The overall order of ssl genes on an S. aureus chromosome is conserved, and allelic forms of individual ssl genes have been identified in different strains. The sequence homology

for individual ssl genes ranges from 85% to 100% in different strains. However, 11 ssl genes within a strain have sequence homology from 36% to 67%, suggesting possible selective pressures encountered during infection (Kuroda et al., 2001; Smyth et al., 2007). Every strain of S. aureus examined so far carries a cluster of at least seven of the 11 ssl genes, suggesting that they probably have distinct and possibly nonredundant Avelestat (AZD9668) functions (Arcus et al., 2002; Fitzgerald et al., 2003; Smyth et al., 2007). Expression studies of a family of ssl genes in COL, an early methicillin-resistant S. aureus (MRSA) strain, showed that they are upregulated during the stationary phase like other exotoxin genes (Fitzgerald et al., 2003). SSL5 and SSL11 show high structural homology with the chemotaxis inhibitory protein of S. aureus and have been shown to interfere with the interaction between P-selectin glycoprotein ligand-1 and P-selectin, suggesting that S. aureus uses SSL proteins to prevent neutrophil recruitment towards the site of infection (Bestebroer et al., 2007; Chung et al., 2007). The same binding site was also found in SSL2, SSL3, SSL4, and SSL6 (Baker et al., 2007). SSL7 and SSL9 interact with two separate cell surface ligands of human antigen-presenting cells (monocytes and dendritic cells), leading to internalization by these cells, and may thus play a role in the modulation of host immunity against S.