A New Class of Molecules from Staphylococcus Species Affects Quorum Sensing and Growth of Gram-Negative Bacteria

Abstract

This thesis addressed bacterial communication between Gram positive and Gram negative bacteria. The knowledge that many pathogens rely on cell-to-cell communication mechanisms known as quorum sensing, opens a new disease control strategy: quorum quenching. While studying the interaction of staphylococci with Gram-negative bacteria, we came across another communication system in a Staphylococcus intermedius group (SIG) species which can act as a zoonotic pathogen. This is one of the rare examples where Gram-positive bacteria excrete two compounds in comparatively high amounts that suppress the quorum sensing signaling and inhibit the growth of a broad spectrum of Gram-negative beta- and gamma-proteobacteria. The excreted compounds, named yayurea A and B, were isolated from S. delphini and structurally characterized. In vitro studies with the Nacyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds stimulated the LuxN-mediated phosphorylation of LuxU and caused the opposite effects with AHL. Furthermore, growth of yayurea A and B producing S. delphini is not suppressed by respiratory toxins when co-cultured with P. aeruginosa. Taken together, yayureas are presumably involved in self-protection and ensuring competitiveness in natural environments shared with Gram-negatives. In the second part of thesis, the role of protein A in Staphylococcus aureus adhesion to ethylene glycol coated surfaces was investigated. It was found that the coating materials, HS(CH2)11EG3OMe (EG3OMe) and poly-ethylene-glycol (PEG) prevented bacterial adhesion of S. aureus cells. However, pretreatment of EG3OMe and PEG coatings with r-globulins or serum strongly promoted adherence of S. aureus cell. Furthermore, the spa-deletion mutant S. aureus, lacking the IgG binding protein A, showed reduced adherence and pretreatment of S. aureus with serum significantly decreased adherence. These results suggested that r-globulins play a crucial role in promoting S. aureus cells adhesion by its IgG binding proteins. Particularly γglobulins bound to the coated surfaces thus mediating adherence of S. aureus via its protein A. Intercepting this adherence should prove to be useful in preventing biofilm formation.