Pathogens have evolved strategies to interfere with and inactivate host immune attack. Most or even all pathogens express a number of surface protein, which bind host immune regulators and effector proteins that aid in inactivation of host immune attack. A wide range of pathogens express CRASP- proteins (complement regulator acquiring surface proteins) which bind host complement regulators Factor H, FHL-1 and FHR-1, as well as plasminogen and also additional extra cellular matrix components. Attached to the microbial surface these host effector proteins are functionally active and cause inhibition of complement activation, allow degradation of extracellular matrixes and fibrinolytic activity. Although the pathogen CRASP proteins have identical and highly similar features, ie. binding host effector proteins at the same site(s), they lack common sequence or binding motifs. 

In addition CRASP proteins show a high degree of sequence diversity and variation, suggesting that despite their common binding features, these microbial immune escape proteins display a strain specific variations. Such a variability is effective for antigen variation in order to prevent immunoglobulin binding.

At present four CRASP- proteins of Candida albicans are identified and three proteins which were expressed recombinantly bind Factor H and plasminogen. The sequences of these various Candida CRASP proteins are analyzed in clinical isolates, derived from distinct sites and infections, in order to confirm genetic polymorphisms and sequence variations.

Collaborations

Dr. Christine Hipler, Friedrich Schiller University Jena
Prof. Peter Mayser, University of Giessen