Identification of an immunomodulating metalloprotease of Pseudomonas aeruginosa (IMPa).
Phagocytosis by neutrophils is the essential step in fighting Pseudomonas infections. The first step in neutrophil recruitment to the site infection is the interaction of P-selectin (on endothelial cells) with P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils. Pseudomonas aeruginosa secretes various proteases that degrade proteins that are essential for host defence, such as elastase and alkaline protease. Here we identify PA0572 of P. aeruginosa as an inhibitor of PSGL-1 and named this secreted hypothetical protease immunomodulating metalloprotease of P. aeruginosa or IMPa. Proteolytic activity was confirmed by cleavage of recombinant and cell-surface expressed PSGL-1. Functional inhibition was demonstrated by impaired PSGL-1-mediated rolling of IMPa-treated neutrophils under flow conditions. Next to PSGL-1, IMPa targets CD43 and CD44 that are also involved in leucocyte homing. These data indicate that IMPa prevents neutrophil extravasation and thereby protects P. aeruginosa from neutrophil attack.
Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands. b.w.bardoel@umcutrecht.nl
Bart W
BW
Bardoel
Dennis
D
Hartsink
Mignon M
MM
Vughs
Carla J C
CJ
de Haas
Jos A G
JA
van Strijp
Kok P M
KP
van Kessel
D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D020134:Catalytic Domain; D002448:Cell Adhesion; D002478:Cells, Cultured; D017124:Conserved Sequence; D017077:Culture Media, Conditioned / Q000737:chemistry; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D036904:Leukocyte Rolling; D051917:Leukosialin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000502:physiology; D020539:Sequence Analysis, Protein; D012794:Sialic Acids / Q000378:metabolism
D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D051917:Leukosialin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; C465014:SPN protein, human; D012794:Sialic Acids; D045726:Metalloproteases