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Journal of Bacteriology, February 2007, p. 1231-1237, Vol. 189, No. 4
0021-9193/07/$08.00+0 doi:10.1128/JB.01155-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes
Aaron F. Carlin,1,4,5
Amanda L. Lewis,1,4
Ajit Varki,2,3,4 and
Victor Nizet1,4,6*
Department of Pediatrics, Division of Pharmacology and Drug Discovery,1
Department of Medicine,2
Department of Cellular and Molecular Medicine,3
Glycobiology Research and Training Center,4
Biomedical Sciences Graduate Program,5
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 920936
Received 28 July 2006/
Accepted 13 September 2006
Group B Streptococcus (GBS) is classified into nine serotypes that vary in capsular polysaccharide (CPS) architecture but share in common the presence of a terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely resembles that of cell surface glycans found abundantly on human cells. CD33-related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on host leukocytes that engage host Sia-capped glycans and send signals that dampen inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia as a form of molecular mimicry limiting the activation of an effective innate immune response. In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia- and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by O acetylation has recently been recognized, and we further show that the degree of O acetylation can markedly affect the interaction between GBS and hSiglec-5, -7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation.
* Corresponding author. Mailing address: Division of Pharmacology and Drug Discovery, University of California, San Diego School of Medicine, Cellular and Molecular Medicine East, Room 1066, 9500 Gilman Drive, Mail Code 0687, La Jolla, CA 92093-0687. Phone: (858) 534-9760. Fax: (858) 534-5611. E-mail:
vnizet{at}ucsd.edu.
Published ahead of print on 22 September 2006.
Journal of Bacteriology, February 2007, p. 1231-1237, Vol. 189, No. 4
0021-9193/07/$08.00+0 doi:10.1128/JB.01155-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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