In order to cause colonization and invasive disease, pathogenic bacteria secrete
proteins that modulate host immune defences. Identification and characterization of these
proteins leads to a better understanding of the
pathological processes underlying infectious and inflammatory diseases and is essential in the development of new strategies for their prevention and treatment. Current techniques to functionally characterize these
proteins are laborious and inefficient. Here we describe a high-throughput functional selection strategy using phage display in order to identify immune evasion
proteins. Using this technique we identified two previously uncharacterized
proteins secreted by Staphylococcus aureus, SElX and SSL6 that bind to neutrophil surface receptors. SElX binds PSGL-1 on neutrophils and thereby inhibits the interaction between PSGL-1 and
P-selectin, a crucial step in the recruitment of neutrophils to the site of
infection. SSL6 is the first
bacterial protein identified that binds CD47, a widely expressed
cell surface protein recently described as an interesting target in anti-
cancer therapy. Our findings provide new insights into the pathogenesis of S. aureus
infections and support phage display as an efficient method to identify bacterial secretome
proteins interacting with humoral or cellular immune components.