Adherence ofStaphylococcus aureusto Endothelial Cells: Influence of Capsular Polysaccharide, Global Regulatoragr, and Bacterial Growth Phase

Abstract

The adherence of Staphylococcus aureus to human endothelial cells (EC) is probably an important step in the pathogenesis of systemic staphylococcal infections. We examined the influence of type 5 capsular polysaccharide (CP5) production, the global regulator agr, and the bacterial growth phase on S. aureus adherence to EC. Whereas S. aureus Newman showed maximal adherence to EC in the logarithmic phase of growth, an isogenic agr mutant showed maximal adherence in the stationary growth phase. S. aureus adherence to EC and CP5 expression were negatively correlated: a mutation in the agr locus diminished CP5 production and led to increased adherence. Likewise, induction of CP5 expression by addition of NaCl to the growth medium resulted in reduced staphylococcal adherence to EC. S. aureus Newman cells that adhered to EC did not express CP5. A Newman cap5O mutant was acapsular and showed significantly greater adherence to EC than the parental strain did (P < 0.005). Complementation of the cap5O mutation in trans restored CP5 expression and reduced EC adherence to a level similar to that of the parental strain. The enhanced adherence shown by the cap5O mutant was similar in magnitude to that of the agr mutant or the cap5O agr double mutant. Cells of the cap5O mutant and cap5O agr double mutant harvested from stationary-phase cultures adhered significantly better than did cells harvested in the exponential growth phase. These data are consistent with the postexponential and agr-independent expression by S. aureus of at least one putative EC adhesin, whose binding domain may be masked by CP5.Staphylococcus aureus is responsible for a broad range of human diseases, including foreign body infections, bacteremia, abscesses, and wound infections (41). The ability of S. aureus to adhere to extracellular matrix proteins is thought to be essential for colonization and the establishment of infections (17, 41, 52). The interaction of S. aureus with endothelial cells (EC) may play a major role in the pathogenesis of endovascular infections, including endocarditis and metastatic infections (26,41).S. aureus can express several cell wall-associated adhesins specific for recognizing matrix proteins; these adhesins are referred to as MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) (52). MSCRAMMs with specific binding activity toward fibronectin (31, 62), fibrinogen (45, 47), and collagen (53) have been cloned and biochemically characterized. Whether MSCRAMMs are also responsible for the adherence of S. aureus to host cells is still unclear. A role for fibronectin-binding proteins in staphylococcal adherence to bovine epithelial cells (13) and mammary gland cells (36) was recently described; however, other factors were also postulated to mediate epithelial cell adherence (13).The expression of most cell wall adhesins and extracellular virulence determinants in S. aureus is coordinately regulated during the growth cycle (57). Some of the growth cycle-dependent expression patterns can be attributed to the ...

Anagr-Like Two-Component Regulatory System inLactobacillus plantarumIs Involved in Production of a Novel Cyclic Peptide and Regulation of Adherence

“…If the surface polysaccharide operon codes for capsular (membrane-associated) rather than excreted exopolysaccharides, shielding of adhesion factors by capsular polysaccharides could explain our findings. Such shielding has also been observed in S. aureus and might explain our observations, with respect to the reduced glass adherence of the lamA mutant (43). Finally, there are reports on surface characteristics being dependent on the relative levels of expression of different lipopolysaccharides in Pseudomonas aeruginosa, which influence adherence properties to hydrophilic and hydrophobic surfaces (31).…”

The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

“…However, for the same reason, it can also mask other surface components required for staphylococcal pathogenesis. Indeed, it has been shown that capsule impedes the initial attachment of S. aureus to endothelial cells by masking the adhesins (Pohlmann-Dietze, 2000). Thus, the organism needs to regulate capsule production according to requirements at various stages of the infection process.…”

The N-terminal A Domain of Fibronectin-binding Proteins A and B Promotes Adhesion of Staphylococcus aureus to Elastin

“…Transcription of the fnb genes is restricted to the early exponential phase of growth (19) under the control of Agr and SarA (23,24). Fibronectin binding activity is lost as cultures enter stationary phase due to degradation of both FnBPA and FnBPB by V8 serine protease (25) and masking of the proteins by capsular polysaccharide (26). The A domains of FnBPA and FnBPB are 45% identical.…”