The Staphylococcus aureus bacteria is known to cause pustules and mild wound infections. Sometimes these bacteria also cause life-threatening infections. S. aureus produces a whole range of proteins that help the bacteria to enter and survive in the host. One of these proteins is “CHIPS” (Chemotaxis Inhibitory Protein of S. aureus). CHIPS inhibits the migration of white blood cells from the bloodstream to the place of infection by blocking two receptors on the surface of white blood cells: the C5a receptor and the formylated peptide receptor. In this way, CHIPS inhibits the immune system. In some diseases, the immune system is over-activated, for example, following a heart attack or in autoimmune diseases. In such cases, the damage inflicted by the immune system has to be checked. If we can unravel exactly how CHIPS works, this could lead to an entirely new class of anti-inflammatory drugs based on bacterial proteins.
Pieter-Jan Haas studied various S. aureus proteins, and also studied whether CHIPS causes side effects. Although this was not the case in animals, even low dosages produced allergic reactions in healthy human volunteers. In spite of the negative effects, Haas shows that CHIPS can activate white blood cells in the presence of anti-CHIPS antibodies. So, if it is possible to manufacture a CHIPS protein that is no longer recognized by antibodies, this will cause fewer side effects. Using a phage library, Haas found ways to make a CHIPS protein that inhibits inflammations without causing allergic reactions.
Pieter-Jan Haas
Staphylococcal Drug Discovery
PhD advisor: Prof. J. Verhoef
Co-advisor 1: Dr. C.J.C. de Haas
Co-advisor 2: Dr. K.P.M. van Kessel
Co-advisor 3: Dr. J.A.G. van Strijp