Modulation of Staphylococcus epidermidis adhesion and biofilm formation by specific biomaterial surfaces

Medicine?s tremendous progress in recent decades is closely linked to the ever increasing use of biomaterial implants, that is, artificial devices which are implanted into patients? tissues, such as some types of catheters (or large ?drips?) in blood vessels, artificial joints and heart valves, cardiac pacemakers, artificial intraocular lenses, and shunts in the brain. Infection is a major complication of the use of such devices causing major suffering and mortality for the affected patients, and significant costs for the health care system and society in general. Once the devices become infected it is very difficult to eradicate the infection, and often the devices must be removed again, and further procedures undertaken to replace them. In some cases replacement procedures, as well as the infection itself, carries very high risks to the patient. The organism causing these infections most frequently, namely, Staphylococcus epidermidis, has risen from rare obscurity as a pathogen to be one of the five major causes of health-care associated infection in line with MRSA, Clostridium difficile, and other antibiotic resistant organisms. Staphylococcus epidermidis has a particular propensity to adhere to, or colonise, biomaterial surfaces. Better understanding of the interaction of this bacterium with biomaterial surfaces, and the changes in the properties of the organisms during process is urgently needed. We have recently found that different biomaterials enhance expression of the mechanisms involved in bacterial colonisation in measurably different ways. We seek to better understand these processes, which may lead to the rational development and evaluation of biomaterials less prone to colonisation and infection. The reduction of the number of biomaterial-related infections through these new developments by only a few percent could prevent unnecessary incapacity and sufferings for thousands of patients, not to mention large cost savings.

Critical to the pathogenesis of biomedical implant-associated infections, most frequently caused by Staphylococcus epidermidis, is the ability of the bacteria to adhere to the biomaterial surface and then form a biofilm, thereby evading the host?s immune system and antibiotics. Contact of S. epidermidis with biomaterial surfaces causes alterations of expression of adhesins and biofilm factors, but these changes are not well characterised, although they are critical in the establishment of infection. Preliminary results from electron micrographs and immunofluorescence analysis indicate that expression of intercellular adhesive properties differ significantly on attachment of S. epidermidis to different biomaterials like titanium or stainless steel. Therefore, we will study expression of factors functional in biofilm accumulation such as the intercellular polysaccharide adhesin (PIA), and proteinaceous intercellular adhesins Aap and Embp. Quantitative changes and alterations in their functional status on three different metal biomaterials will be studied. As additional surface exposed staphylococcal proteins may contribute significantly to the early colonisation phase we will characterise their expression in a systematic way using immunochemical as well as transcriptional analysis with microarray and qRT-PCR methods. The expression of adhesion factors on native and extracellular matrix protein-modified surfaces will be compared. The importance of the observed differences will be confirmed by studying expression patterns of a number of S. epidermidis strains from different forms of device-related infection. Translational applications of this new knowledge may ultimately channel into the rational development and evaluation of biomaterials less prone to colonisation and infection. This application specifically proposes to:

1. Identify and quantify the influence of biomaterial surfaces on adhesion and expression of S. epidermidis adhesins and intercellular adhesive mechanisms (Aims 1-4)
2: Compare S. epidermidis adhesion and expression of adhesins and intercellular adhesive mechanisms on ECM-modified and native biomaterial surfaces (Aim 5)
3: Determine if similar expression patterns are observed in a number of S. epidermidis strains from different forms of prosthetic device infection (Aim 6)