How complement kills bacteria: A pore way to die

Abstract

Infections with bacteria form an increasing threat for human health. This is mainly due to the fact that bacteria develop mechanism to resist killing by existing antibiotics. In order to find alternatives to treat infections with bacteria, it is crucial to understand how our own immune system kills these bacteria. This knowledge could contribute to the development of new therapies against bacteria, where we use the immune system of the patient to efficiently attack invading pathogens. In this thesis, we unraveled part of the mechanism with which the complement system, an important player of the immune system, kills bacteria. The complement system gets activated by antibodies, which are proteins that specifically bind the surface of invading bacteria. We show how the complement system forms pores in the bacterial cell wall that damage the cells in such a way that these bacteria die. We also show that the immune system can sensitize bacteria for existing antibiotics, which were thought to be ineffective since these were tested in the absence of the immune system. The knowledge described in this thesis could help in future research, in which we want to engineer antibodies that efficiently activate the complement system and stimulate the formation of pores that kill bacteria. These antibodies could then be combined with existing antibiotics that are more efficient in the presence of an active complement system.