The majority of human infections are caused by biofilms. The biofilm mode of growth enhances the pathogenicity of Staphylococcus spp. considerably, because once they adhere, staphylococci embed themselves in a protective, self-produced matrix of extracellular polymeric substances (EPSs). The aim of this study was to investigate the influence of forces of staphylococcal adhesion to different biomaterials on icaA (which regulates the production of EPS matrix components) and cidA (which is associated with cell lysis and extracellular DNA [eDNA] release) gene expression in Staphylococcus aureus biofilms. Experiments were performed with S. aureus ATCC 12600 and its isogenic mutant, S. aureus ATCC 12600 ⌬pbp4, deficient in peptidoglycan cross-linking. Deletion of pbp4 was associated with greater cell wall deformability, while it did not affect the planktonic growth rate, biofilm formation, cell surface hydrophobicity, or zeta potential of the strains. The adhesion forces of S. aureus ATCC 12600 were the strongest on polyethylene (4.9 ؎ 0.5 nN), intermediate on polymethylmethacrylate (3.1 ؎ 0.7 nN), and the weakest on stainless steel (1.3 ؎ 0.2 nN). The production of poly-N-acetylglucosamine, eDNA presence, and expression of icaA genes decreased with increasing adhesion forces. However, no relation between adhesion forces and cidA expression was observed. The adhesion forces of the isogenic mutant S. aureus ATCC 12600 ⌬pbp4 (deficient in peptidoglycan cross-linking) were much weaker than those of the parent strain and did not show any correlation with the production of poly-N-acetylglucosamine, eDNA presence, or expression of the icaA and cidA genes. This suggests that adhesion forces modulate the production of the matrix molecule poly-N-acetylglucosamine, eDNA presence, and icaA gene expression by inducing nanoscale cell wall deformation, with cross-linked peptidoglycan layers playing a pivotal role in this adhesion force sensing.
Staphylococcus spp. present an important group of potentially pathogenic strains and species. According to estimates by the National Institutes of Health, about 80% of all human infections are caused by biofilms (1). The biofilm mode of growth considerably enhances the pathogenicity of Staphylococcus spp. when the biofilm is formed on the surfaces of biomaterial implants and devices, such as total knee or hip arthroplasties or pacemakers (2). Biofilm formation starts with the adhesion of individual organisms to a substratum surface. Initially, adhesion is reversible, but the bond between an adhering organism and a substratum surface rapidly matures over time to become stronger, and eventually, adhesion is irreversible (3). Adhesion is further enforced through the production of a matrix consisting of extracellular polymeric substances (EPSs) by the adhering organisms, in which they grow and find shelter against the host immune system and antibiotic treatment. The EPS composition largely depends on the bacterial strains and environmental conditions, but major components of EPSs across differen...