Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins (Blood, 2009, 113:328-337)

報告日期: 2009/03/24
報告時間: 16:00/16:50
報告學生: 王雅惠
講評老師: 徐麗君

Staphylococcal SSL5 inhibits leukocyte activation by

chemokines and anaphylatoxins


Bestebroer J, van Kessel KP, Azouagh H, Walenkamp AM, Boer  IG, Romijn RA, van Strijp JA, de Haas CJ

Blood, 2009, 113:328-337


Speaker: 王雅惠

Commentator: 徐麗君老師

Time: 2009/03/ 24 16:00

Place: Room 602



Staphylococcus aureus can secrete several virulence factors to modulate host immune response for establishing severe infection. Staphylococcal superantigen-like (SSL) protein are a family of exotoxins with structural homology to superantigens but with generally unknown functions. Recently, the authors found SSL5 can bind to cell surface P-selectin glycoprotein ligand-1 (PSGL-1) dependently of sialyl LewisX  and inhibit P-selectin-mediated neutrophil rolling toward the infection sites. In this paper, they further demonstrated SSL5 inhibits neutrophil activation by chemokines and anaphylatoxins, whereas activation by other chemoattractants is not affected. Competition experiments and transfection studies showed that SSL5 targets chemokine and anaphylatoxin receptors by binding glycosylated N-termini of all G protein–coupled receptors (GPCRs) but only blocks stimuli of ligands that require binding to N-termini for activation. SSL5 also can scavenge chemokines to cells independently of specific receptors only through glycosylation. In conclusion, SSL5 binds PSGL-1, GPCRs and chemokines, and thereby it inhibits leukocyte rolling, activation and chemotaxis to interfere with host defense. Thus SSL5 is a potent modulator of S aureus that targets several critical stages of leukocyte extravasations and is a potential new therapeutic compound for inflammatory diseases.



1.   Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling. Blood. 2007;109:2936-2943

2.      Crystal structures of the staphylococcal toxin SSL5 in complex with sialyl Lewis X reveal a conserved binding site that shares common features with viral and bacterial sialic acid binding proteins. J Mol Biol. 2007;374:1298-1308.