Staphylococcus aureus proteins SSL6 and SElX interact with neutrophil receptors as identified using secretome phage display.
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.
Department of Medical Microbiology, University Medical Center Utrecht, PO G04.614, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Cindy
C
Fevre
Jovanka
J
Bestebroer
Mirjam M
MM
Mebius
Carla J C
CJ
de Haas
Jos A G
JA
van Strijp
J Ross
JR
Fitzgerald
Pieter-Jan A
PJ
Haas
D001426:Bacterial Proteins / Q000378:metabolism*; D051928:CD47 Antigen; D061505:Cell Surface Display Techniques / Q000379:methods*; D054884:Host-Pathogen Interactions; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000502:physiology*
D001426:Bacterial Proteins; D051928:CD47 Antigen; C497894:CD47 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084882:P-selectin ligand protein