The functional class most frequently represented among these genes were those involved in transport and metabolism of amino acids (e.g., hutH, arcB-D, etc.), nucleotides (e.g., purA, deoD, tmk, etc.), inorganic ions (e.g., sirA-C, phnB, phnC, phnE, etc.), carbohydrate (e.g., bglA, fruA, fruB, etc.).
The transcripts of the accessory gene regulator agr system (agrA, agrB, and agrC) were downregulated (8- to 19-fold) while sarV, a member of the SarA protein family, increased 6.4-fold. The gene expression of the genes of the Sigma B operon (sigB, rsbW, and rsbV) that have been shown to respond to environmental stresses decreased 2- to 4-fold. Also, the gene expression of two different genes encoding TetR family transcription regulators was upregulated. TetRs are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters (12). Two genes encoding MarR family transcription regulators were upregulated 10.4-fold while the other was downregulated 2.46-fold. The members of the MarR family of transcription factors are critical for bacterial cells to respond to chemical signals and to convert such signals into changes in gene activity (13). The MsrR transcriptional regulator which affects resistance to methicillin and teicoplanin was upregulated by 2.3-fold. LexA repressor that regulated the expression of the SOS gene was downregulated by 3.4-fold. The srrA genes of the two-component regulatory system (TCRS) positively influence the transcription of genes involved in aerobic respiration in response to changes in respiratory flux were downregulated by 3-fold.
The gene expression of several S. aureus genes encoding virulence factors changed during the first 24 hours of skin infection. The expression of fnbA increased by 2.3-fold as well as the gene encoding fibronectin-binding proteins (e.g., fnbA, fnbB, sdrC, sdrD, sdrE, SAUSA300_1028, and SAUSA300_1029) that showed substantially increased mRNA levels (2- to 125-fold). The sarA locus up-regulates the expression of many cell wall proteins including FnbA. Fibronectin-binding proteins contribute to the colonization and infection of the host by S. aureus via adhesion to fibronectin present in the extracellular matrix of the tissues. They play a role in the virulence of S. aureus skin abscess infection, infective endocarditis, bacteremia, sepsis, pneumonia, and foreign body infections (14).
The gene expression of spa that had been described previously as down-regulated by sarA locus (15), increased in the skin abscess by 4.0-fold. Protein A effectively blocks the formation of IgG hexamers and subsequent complement activation (16). The gene expression of clfA, a cell surface-associated protein that binds fibrinogen promoting S. aureus colonization of host tissues and biomedical devices under physical stress (17), was downregulated by 6.5-fold. The gene expression of hemolysin gamma A gene (hlgA, SAUSA300_2365) that have been described previously to require both Sae and Agr (18), in this model increased 20.8-fold. Actually, hlgB (SAUSA300_2367) and hlgC (SAUSA300_2366) increased by 76.3- and 27.4-fold, respectively. Haemolysin gamma A, B, and C (HlgABC) displayed cytotoxicity to monocytes and natural killer cells (19).
The expression of genes encoding coagulase (Coa), and two von Willebrand factor binding proteins (vWbp) with coagulase activity that are required for septicemia and abscess formation (20) increased 12- to 34-fold. Coa is involved in the virulence of S. aureus. The fibrinogen-binding motifs also found in coagulase block neutrophil αMβ2 adherence to fibrinogen and attract fibrinogen to the bacterial surface, forming capsule-like structures that block phagocytosis (21).
The gene expression of a gene (scin) belonging to the family of S. aureus complement inhibitory proteins increased more than 57-fold. They share a common domain of three helices at the C3 binding region (22) and are implicated in the S. aureus evasion of the complement-mediated immune response. Surprising the gene efb which encodes another complement inhibitory protein was unaffected. Also, gene expression of emp that encodes a protein with a fibrous structure that binds to different extracellular matrices proteins increased 11.7-fold (23). Emp plays an important role in low-iron-induced biofilm formation (24). The expression of the gene sasC encoding the S. aureus surface protein C which is involved in cell aggregation and biofilm accumulation (25) increased by 10-fold. The gene expression of gene encoding SpoVG which is a repressor of the expression of sasC, decreased by 8.3-fold.
The gene expression of genes encoding exotoxins increased. For example, the mRNA level of genes (SAUSA300_0396, _0397,_0399, _0400, _0401,_0402, _0404, _00407 and SAUSA300_1059 to _1061) encoding staphylococcal superantigen-like (SSL) proteins increased from 5.0- to 125-fold. SSL proteins have been shown to help S. aureus to escape from the protective adaptive immune response of the host and thus may contribute to bacterial pathogenicity (26,27). The gene expression of several multidrug resistance genes was upregulated like fmtB methicillin resistance proteins (SAUSA300_2109 and SAUSA300_2110) that increase by 42.5- to 38.2-fold, multidrug resistance protein B (SAUSA300_2298) that increased by 12.2-fold, and multidrug resistance protein A defense mechanisms/virulence (SAUSA300_2299) that increased 37.0-fold.