Staph is a bacteria that lives on the skin and can cause all kinds of infections. This bacteria can become resistant to antibiotics because it forms a slime layer – biofilm – that prevents antibiotics from reaching the bacteria. Doctor-researcher Lisanne de Vor of UMC Utrecht showed that certain antibodies (linked to specific enzymes) can break down biofilm, making resistant bacteria sensitive to antibiotics again. On 4 November she obtained her doctorate on this subject.
Skin inflammations, heart valve inflammation and implant infections. These are nasty infections that the staphylococcus bacteria can cause. And when antibiotics can no longer reach this bacteria, the treatment of such infections becomes increasingly complicated. Biofilm formation on the surface of a medical implant, such as a heart valve or prosthesis, is also a known complication of staphylococcal infections. In a biofilm, bacteria are protected against antibiotics and immune cells by a self-made layer of sugars, proteins and DNA. Because existing treatments are often insufficiently effective against staphylococcal infections, there is a need to develop new treatment options, such as antibody therapy. “Through our research, we have a better understanding of how antibodies can stimulate staphylococcal phagocytosis. We have also gained more insight into the usefulness of antibodies against biofilm-related infections. These findings can contribute to the development of antibody therapy against staphylococcal infections,” says Lisanne de Vor of the Department of Medical Microbiology at UMC Utrecht.
Biofilm
Antibodies
Antibody therapy is currently mainly used for the treatment of cancer or autoimmune diseases, but little is known about whether antibody therapy can also be useful in the treatment of infectious diseases. In her PhD research, Lisanne investigated how antibodies can be used to treat infections with S aureus in S. epidermidis to combat.
Protective layer
Antibodies can bind specifically to foreign structures, such as bacteria, and designate them as ‘dangerous’ for the immune system. To date, no antibodies are known that can recognize biofilm. Lisanne and colleagues have shown that antibodies can recognize staphylococci in biofilm, despite the protective slime layer that surrounds the bacteria. This means that antibodies could potentially be used to develop antimicrobial therapies for implant-related infections.
It was already known from previous studies that bacteria can become sensitive again to antibiotics and immune cells after they have been ‘liberated’ from a biofilm. Specific enzymes that can break down the protective mucus layer are therefore of great importance, but are difficult to administer to patients. To investigate the practical utility of antibodies in this regard, the researchers linked antibodies to these specific enzymes. In a in vitro study, Lisanne and her colleagues showed that the fusion proteins retained the ability to bind bacteria. The fusion protein was also capable of inhibiting biofilm formation S aureus prevent and break down already formed biofilm.
Custom antibodies
In another in vitro study, Lisanne also showed that adapted antibodies, which were originally developed to strengthen the immune system against tumor cells, may also be used to treat staphylococcal infections. Antibodies with this adaptation can activate even the still underdeveloped immune system of newborns to eliminate bacteria. These findings show that antibodies could promote the ‘eating’ (phagocytosis) of bacteria by immune cells and could therefore be useful in the treatment of neonatal bloodstream infections due to infection with S. epidermidis.
Promotion
Lisanne de Vor (1993, Nieuwegein) defended her thesis on 4 November 2022 at Utrecht University. The title of her dissertation is “Staphylococcal infections – can antibodies help?Promotors were Prof. Dr. Suzan Rooijakkers (Department of Medical Microbiology, UMC Utrecht) and Prof. Dr. Harrie Weinans (Department of Orthopedics, UMC Utrecht). Co-supervisor was Dr. Kok van Kessel (Department of Medical Microbiology, UMCUtrecht). Lisanne continues her career as a postdoc at the Bacteria & Complement research group of Prof. Suzan Rooijakkers at UMC Utrecht.
Questions, comments or tips for the editors?