Medical implants have been optimised with micro- and nano-rough surfaces for enhanced bone intergration; however, such surfaces also promote the unwanted adhesion of pathogens, resulting in an inflammatory response, causing the loss of supporting bone, and ultimately leading to implant failure. Once a biofilm has formed, it can be very difficult to clinically remove it, which may result in recurring infection and progressive damage to both implant and supporting bone.
The model system for this grant, Actinobacillus/Aggregatibacter actinomycetemcomitans (A.ac.) is a Gram-negative bacterium associated with aggressive periodontitis (an inflammatory condition that causes the degradation of the tissues surrounding the teeth) and with failing implants. Complications of A.ac. infections include endocarditis (inflammation of the inner tissues of the heart, most commonly affecting the aortic valve), brain and subcutaneous abscesses, and osteomyelitis (bone infection). The mortality rate from A.ac. endocarditis is approximately 18%. It is therefore desirable to prevent an infection with A.ac. before it can gain the resistance advantages from biofilm formation and maximised pathogenicity.
Understanding the adhesion mechanisms of A.ac. and of its major adhesins (the molecules that mediate adhesion to surfaces) can help to understand the adhesion and biofilm formation strategies of a whole library of pathogens. The similarity between these adhesins implicates the potential to prevent the adhesion of further pathogens by minor modification to the disruption mechanism for A.ac. adhesion.
We intended to drive the development of novel antibacterial surfaces through creating more detailed knowledge about bacterial adhesion mechanisms. Bactericidal approaches promote the evolution of resistance mechanisms, and generally anti-adhesive surfaces are of limited use in the medical field, since such surfaces also prohibit host-tissue integration. Anti-adhesive surface modifications therefore needed to become more specific to achieve selective adhesion.
We therefore wanted to establish a bottom-up approach, starting with the assay development for molecular biology studies of bacterial adhesion factors, and of their interaction with surfaces. The aim was to create a feedback-loop that translates assay results into increasingly specific surface modifications, using iterative test runs that combine identified anti-adhesive conditions for a particular adhesion protein. Novel approaches to assay development and rapid translation of fundamental research into applied surface modifications were expected from the collaboration between a materials science group (BIOMAT: Department of Biomaterials) and a molecular biology group (IBV: Department of Biosciences). The collaboration between these groups is a unique opportunity to obtain both an understanding of adhesin function and the direct implementation of this knowledge to novel surface modifications. This project therefore promoted interdisciplinary expertise and has the strong potential to generate further multidisciplinary collaborations with opportunities for interdisciplinary training.
