Complement evasion by human pathogens

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Abstract
The human complement system has a pivotal role in the recognition, opsonization and elimination of microbial intruders. This functionality is maintained by a well-balanced interaction network of serum proteins and cell-surface receptors. Over thousands of years of co-evolution, many microorganisms have developed specific complement-evasion strategies to escape the attack of the immune system. Although some of these strategies are highly specific for a single species, others are shared more broadly among bacteria, viruses, fungi and parasites. The most prevalent complement-evasion mechanism seems to be the capture of soluble host complement regulators on the microbial surface or the expression of their structural mimics. However, the inactivation of complement components by proteolytic degradation or specific inhibition of essential functional sites is also frequently observed. Staphylococcus aureus has a particularly wide and diverse arsenal of complement-evasion proteins, many of which have been discovered only recently. These numerous evasion strategies could contribute to the high virulence of this bacterium. Structural biology is an indispensable tool for characterizing the structure and function of complement-evasion proteins. Recent publications of the co-crystal structures of evasion proteins with their human targets have allowed an even deeper insight into the molecular basis of these escape mechanisms. The rapid increase in the structural and functional understanding of complement evasion could serve as an important starting point for the development of antimicrobial or complement-targeting therapeutics.