The role of adsorbed protein conformation in the recognition and attachment of Staphylococcus epidermidis to implant surfaces (Nasar Khan, Aslan Husnu)
In the context of implants, bacteria attach to the surface of an implant via receptor-ligand interactions with adsorbed human proteins. However, it is puzzling how this is possible because the same proteins are available in solution in the blood stream where the bacteria are suspended. One would expect that the receptor proteins on the bacterial cell would be occupied with ligands available in solution before the cell arrives at the surface of the implant. We recently observed that Staphylococcus epidermidis, which has a receptor protein for human fibronectin, will only interact with fibronectin adsorbed to a polystyrene surface, and not fibronectin in solution (unpublished results). I hypothesize that this observation can be explained by the conformation change that fibronectin undergoes when adsorbing to a surface. Proteins undergo adsorption-induced conformation changes, and these changes could expose binding sites that are not available when the protein is in solution.
The surface chemistry of materials affect the conformation of adsorbed proteins, and this has indeed been shown for fibronectin, which takes different conformations on different materials and even initiates fibrillogenesis on some materials. If this hypothesis is true, it challenges the way we previously studied receptor-ligand interactions with relevance to biofilm formation, and it presents a new opportunity for developing materials that steer the protein conformation of adsorbed proteins away from promoting bacterial attachment.
The project is supported by the Carlsberg Foundation's Distinguished Associate Professor Fellowship (3.7 mill DKK)
DNA sequencing for analysis of microbial contamination in raw milk
High quality dairy products start with high quality raw milk. The total number of bacteria in raw milk is monitored on a bi-weekly basis, and when contamination occurs the farmer initiates procedures to eliminate the problem. We hypothesize that if the farmer knows which bacteria that are responsible for the contamination, one would be able to tailor how the problem is approached.
In this project, we use next-generation sequencing of 16S rRNA amplicons to determine the microbial community composition in raw milk from 30 different dairy farms. We follow the changes over time during a 2 months period, and correlate the community composition with counts of total bacteria and thermoresistant bacteria. From knowledge about the process parameters at the farm, we seek to identify key issues that either lead to contamination in general, or a type of contamination that is not resolved by standard methods.
The Holy Grail in biofilm research is to develop new control strategies that target biofilm formation, rather than subsequent removal, by hindering the biological processes responsible for biofilm formation. Development of such strategies requires a detailed and fundamental understanding of the biological mechanisms controlling bacterial attachment. Biomolecules on the cell surface are central to bacterial attachment as they control the cell-to-surface and cell-to-cell interactions leading to attachment. These interactions include both non-specific physicochemical interactions, and specific adhesin-receptor binding. Although we know some of the biomolecules involved, the exact mechanism behind their function remains elusive for many.
The vision of this project is to determine how particular biomolecules on the cell surface regulate the cell surface properties and mediate biofilm formation. The objective missions are:
1) To identify biomolecules that control surface properties and attachment of bacterial cells, and
2) To determine the specific mechanisms with which such biomolecules assist biofilm formation.
The project is supported with 8.6 mill DKK from the Danish Council for Independent Research (Sapere Aude program) (2012-2016)
Targeting of implant-associated biofilm infections by super-paramagnetic iron oxide particles (Cindy Dreier)
This project develops SPIONS for in vivo use to target and kill biofilm infections associated with biomedical implants.
Collaborators: Guruprakash Subbiahdos (iNANO), Jørgen Kjems (iNANO), Nis Pedersen Jørgensen (AUH), Michael Pedersen (AUH).
The PhD stipend for Cindy Dreier is funded by The Lundbeck Foundation (1.5 mill DKK).
Nanoencapsulation of antibiotics for treatment of biofilm infections (Line Hansen, Pernille Ommen Andersen)
Treatment of biofilm infections remains one of the major unresolved problems in infection microbiology. As bacteria stick to a surface and form a biofilm, e.g. of a medical implant, they become encapsulated in a polymer matrix and enter a physiological state that increases their tolerance to antibiotics dramatically. The infection becomes untreatable because antibiotics cannot be dosed in a concentration that is sufficient to eliminate the biofilm. We propose that a high local concentration of antibiotics can be obtained by targeting encapsulated antibiotics to the biofilm to obtain a high local concentration. This can be achieved by nanoencapsulation of antibiotics in particles with specific receptors that recognize the bacterial cell surface or biofilm matrix components. Partners: Peter Thomsen (BioModics), Jørgen Kjems (iNANO)). The project is supported with 6 mill DKK from the Danish Council for Technology and Production (2015-2018).
Treatment of implant-associated biofilm infections (Nis Pedersen Jørgensen, Sandra Skovdal, Cindy Dreier).
The purpose of this project is to establish a novel animal model of staphylococcal biofilm osteomyelitis (OM) model, and use it to investigate staphylococcal biofilm formation on orthopaedic implants, the role played by regulatory genes and the possible in vivo interaction with antibiotic treatment in a murine model of implant-associated osteomyelitis. In collaboration with Ryosuke Ogaki, we furthermore explore the benefit of antiadhesive polymer brush coatings based on poly-l-lysine grafted with poly-ethylene glycol using a new method for temperature-enhanced grafting. Partners: Jørgen Eskild Petersen (Aarhus University Hospital, main supervisor), Kurt Fuursted (Statens Serum Institut). The PhD project is supported by Aarhus University (HEALTH).
Heat Transfer Effective Anti-Fouling Solutions for Heat Exchange Surfaces (Guruprakash Sabbiahdos, Jonas Jensen, Jakob Ege Friis)
Fouling of heat-exchange surfaces reduces process performance and lifetime, and requires regular cleaning and/or part replacement, resulting in process downtime and increased cost. Managing fouling is the key to control the performance and lifetime of heat exchangers, and remains the major unresolved problem in heat transfer. This project addresses the fouling of heat transfer surfaces in water-based installations.
The vision of this project is to develop novel antifouling solutions that do not compromise heat transfer efficiency. The project builds on two recent developments at Aarhus University in the area of surface functionalization. The first development (by Kim Daasbjerg’s group) is the demonstration that thin organic polymer layers can be covalently attached to metal substrates by electro-grafting followed by surface initiated polymerization. We will develop this technology as a platform to generate robust, dense and multifunctional hydrophilic polymer brush layers by choosing appropriate blends of monomers with specific functional groups. The second development (by Duncan Sutherland’s group) is the demonstration of nanostructured interfaces as a new technology for heat transfer enhancing materials. The small thickness of the polymer coating allow us to merge the two technologies in optimising both heat transfer and fouling resistance. The objective of the project is thus to combine surface structuring with ultra-thin (0.01-1μm) coatings of polymer and/or polyelectrolyte brush layers on stainless steel to obtain a highly hydrated surface that resist fouling without significant loss of heat transfer efficiency.
The 15.4 mill DKK project is supported with 7.7 mill DKK from the Innovation Fund Denmark.
Characterisation of antiadhesive and antibiotic-releasing layer-by-layer coatings (Signe Maria Nielsen, Rikke Christiansen)
Alexander Zelikin’s group at Aarhus University designs and develop layer-by-layer coatings containing active enzymes used to convert pro-drugs to active drugs. We explore the potential for this approach to obtain coatings that release antibiotics when exposed to a pro-drug. The synthesis of antibiotic from within the coating may provide several advantages to treating biofilm infections on coated implants, e.g. delivery of antibiotics to the inner layer of the biofilm, and delivery of a local high concentration of antibiotics at the site of the biofilm infection. The project is a collaboration with Alexander Zelikin.