Cell wall deformation and Staphylococcus aureus surface sensing

Bacterial contaminations are one of the major causes for implant failure and cause significant reduction in patient’s quality of life. Therefore, understanding the underlying factors that contribute to bacteria-biomaterial interactions are of utmost importance for researchers and health care professionals who develop biomaterials and new anti-bacterials. In this context, the aim of this thesis was to evaluate the role of adhesion forces in the response of bacteria to their adhering state. To this end, we used a model pathogen Staphylococcus aureus, common in biomaterial associated infections and several of its isogenic mutants and applied Atomic Force Microscopy (AFM) and Surface Enhanced Fluorescence (SEF) to quantify adhesion forces and cell wall deformation, respectively. Bacterial response was evaluated in terms of gene expression on different biomaterials commonly used in orthopedic implants. Our findings show that S. aureus experiences adhesion forces in the range 1.0 – 5.0 nN on the three biomaterials Stainless Steel (SS), Poly-Methylmethacrylate (PMMA) and Polyethylene (PE) and provide proof of concept that adhesion forces induce cell wall deformation upon adhesion to SS using SEF. At the molecular level we show that, as adhesion forces increase between the bacteria and the substratum, icaA gene expression and the expression of matrix components (Poly-N-acethyglocosamine and eDNA) decreases, suggesting a direct impact of adhesion forces on gene expression. Furthermore, presence of chemical stress nisin (antibiotic) in combination with mechanical stress (adhesion forces), increases the expression of the two-component system nisin-associated-sensitivity-response-regulator (NsaRS) and its downstream transporter NsaAB involved in pumping out nisin. Finally, our results confirm that adhesion forces and subsequent cell wall deformation upon surface adhesion determine the adaptability of S. aureus to the surface it adheres.