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A spectrum of in vivo-expressed Staphylococcus aureus antigens was identified by probing bacteriophage expression libraries of S. aureus with serum samples from infected and uninfected individuals. Eleven recombinant antigenic proteins were produced, and specific antibody titers in a large collection of human serum samples were determined. Significantly increased concentrations of reactive immunoglobulin G (IgG) to 7 antigens were found in serum samples from ill individuals, compared with those in healthy individuals. Significantly higher concentrations of reactive IgG to 4 antigens, including iron-responsive surface determinant (Isd) A and IsdH, were found in serum samples from healthy individuals who were not nasal carriers of S. aureus, compared with those in healthy carriers. Vaccination of cotton rats with IsdA or IsdH protected against nasal carriage. Also, IsdA is involved in adherence of S. aureus to human desquamated nasal epithelial cells and is required for nasal colonization in the cotton rat model. Thus, vaccination with these antigens may prevent S. aureus carriage and reduce the prevalence of human disease.

Resistance to human skin innate defenses is crucial for survival and carriage of Staphylococcus aureus, a common cutaneous pathogen and nasal colonizer. Free fatty acids extracted from human skin sebum possess potent antimicrobial activity against S. aureus. The mechanisms by which S. aureus overcomes this host defense during colonization remain unknown. Here, we show that S. aureus IsdA, a surface protein produced in response to the host, decreases bacterial cellular hydrophobicity rendering them resistant to bactericidal human skin fatty acids and peptides. IsdA is required for survival of S. aureus on live human skin. Reciprocally, skin fatty acids prevent the production of virulence determinants and the induction of antibiotic resistance in S. aureus and other Gram-positive pathogens. A purified human skin fatty acid was effective in treating systemic and topical infections of S. aureus suggesting that our natural defense mechanisms can be exploited to combat drug-resistant pathogens.

SummaryAs an important facet of host-pathogen interaction, Staphylococcus aureus has the ability to adhere to human extracellular matrix (

In order for Staphylococcus aureus to adhere to host extracellular matrix (ECM) substrates, it elicits a wide range of surface proteins. We have characterized a novel ϳ1.1-MDa protein in S. aureus, termed Ebh (for ECMbinding protein homologue), which has homology to other ECM-binding proteins. Ebh consists of several domains, including a large central region with 44 imperfect repeats of 126 amino acids. Expression analysis revealed ebh to be growth phase regulated and repressed by agr. A fragment of the central repeat region of Ebh was cloned, overexpressed, and used in ligand-binding studies to determine Ebh function. The recombinant protein was found to specifically bind human fibronectin. Ebh is produced during human infection since serum samples taken from patients with confirmed S. aureus infections were found to contain anti-Ebh antibodies. Localization studies revealed Ebh to be cell envelope associated and is proposed to form a specialized surface structure involved in cellular adhesion.Staphylococcus aureus is able to cause a wide range of different infections, such as endocarditis, arthritis, and septicemia (55). In order for S. aureus to colonize and disseminate through its host, the bacterium expresses an array of proteins which interact with molecules of the host extracellular matrix (ECM). These bacterial cell surface and extracellular proteins bind to a wide range of host proteins, such as fibronectin (Fn) (15,21,25,42), fibrinogen (Fg) (21,36,40,56), vitronectin (21), collagen (50), thrombospondin (18), bone sialoprotein (51), elastin (8), and von Willebrand factor (16), belying the ability of S. aureus to act as the etiological agent of a variety of pathologies. Fn is an adhesive glycoprotein found on the surface of mammalian cells and in serum (7). Previous studies have implicated staphylococcal Fn-binding proteins with adhesion to different cell types (1,23,37,38,47). Also, they bind Fn, which acts as an invasin, forming a bridge between S. aureus and an integrin on the surface of nonprofessional phagocytes (1,9,23,33,46,48). Most of the ligand-binding proteins that have previously been characterized are found associated with the cell wall and are known as microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) (13). The specific interactions that these adhesins undergo with the ECM, coupled with the fact that they are found on the surface of the cell, means that they may be useful targets for prophylaxis or therapy, e.g., as vaccine components, as targets for passive immunotherapy, or for novel antiadhesive strategies.Recently, the genomes of S. aureus strains N315 and Mu50 have been published (31), and determination of the genomes of five additional strains has either been done or is nearing completion. These studies have revealed the presence of many uncharacterized putative surface proteins. The two largest genes, ebhA and ebhB, encode putative proteins of ca. 722 and 421 kDa, respectively. EbhA shows homology to the major adhesin of Streptococcus defectivus, Emb, a p...

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Economic reform in China has

Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively) killed S. aureus, and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively) and conjugated bile salts (glycocholic and taurocholic acid at 20 mM) at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on S. aureus than conjugated bile salts.