HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 16, 11186-11192, April 21, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/16/11186    most recent M513772200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lewis, A. L. Articles by Nizet, V. Search for Related Content PubMed PubMed Citation Articles by Lewis, A. L. Articles by Nizet, V. Social Bookmarking                      What's this?

The Group B Streptococcal Sialic Acid O-Acetyltransferase Is Encoded by neuD, a Conserved Component of Bacterial Sialic Acid Biosynthetic Gene Clusters^*

Amanda L. Lewis¹, Mary E. Hensler^¶, Ajit Varki^||**, and Victor Nizet^¶2

From the Division of Biological Sciences and the Departments of ^¶Pediatrics, ^||Medicine, and ^**Cellular and Molecular Medicine, and the Glycobiology Research and Training Center, School of Medicine, University of California San Diego, California 92093-0687

Nearly two dozen microbial pathogens have surface polysaccharides or lipo-oligosaccharides that contain sialic acid (Sia), and several Sia-dependent virulence mechanisms are known to enhance bacterial survival or result in host tissue injury. Some pathogens are also known to O-acetylate their Sias, although the role of this modification in pathogenesis remains unclear. We report that neuD, a gene located within the Group B Streptococcus (GBS) Sia biosynthetic gene cluster, encodes a Sia O-acetyltransferase that is itself required for capsular polysaccharide (CPS) sialylation. Homology modeling and site-directed mutagenesis identified Lys-123 as a critical residue for Sia O-acetyltransferase activity. Moreover, a single nucleotide polymorphism in neuD can determine whether GBS displays a "high" or "low" Sia O-acetylation phenotype. Complementation analysis revealed that Escherichia coli K1 NeuD also functions as a Sia O-acetyltransferase in GBS. In fact, NeuD homologs are commonly found within Sia biosynthetic gene clusters. A bioinformatic approach identified 18 bacterial species with a Sia biosynthetic gene cluster that included neuD. Included in this list are the sialylated human pathogens Legionella pneumophila, Vibrio parahemeolyticus, Pseudomonas aeruginosa, and Campylobacter jejuni, as well as an additional 12 bacterial species never before analyzed for Sia expression. Phylogenetic analysis shows that NeuD homologs of sialylated pathogens share a common evolutionary lineage distinct from the poly-Sia O-acetyltransferase of E. coli K1. These studies define a molecular genetic approach for the selective elimination of GBS Sia O-acetylation without concurrent loss of sialylation, a key to further studies addressing the role(s) of this modification in bacterial virulence.

Received for publication, December 27, 2005 , and in revised form, February 6, 2006.

^* This work was funded by National Institutes of Health Grants R01HD051796 (to V. N.), R01GM32373 (to A. V.), and P01HL57345 (to A. V.) and an American Heart Association Established Investigator Award (to V. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by University of California, San Diego Institutional National Institutes of Health Training Grant 5 T32 DK07202.

² To whom correspondence should be addressed. Tel.: 858-534-7408; Fax: 858-534-5611; E-mail: vnizet{at}ucsd.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. L. Lewis, H. Cao, S. K. Patel, S. Diaz, W. Ryan, A. F. Carlin, V. Thon, W. G. Lewis, A. Varki, X. Chen, et al. NeuA Sialic Acid O-Acetylesterase Activity Modulates O-Acetylation of Capsular Polysaccharide in Group B Streptococcus J. Biol. Chem., September 21, 2007; 282(38): 27562 - 27571. [Abstract] [Full Text] [PDF]

				E. Severi, D. W. Hood, and G. H. Thomas Sialic acid utilization by bacterial pathogens Microbiology, September 1, 2007; 153(9): 2817 - 2822. [Abstract] [Full Text] [PDF]

				A. K. Bergfeld, H. Claus, U. Vogel, and M. Muhlenhoff Biochemical Characterization of Thepolysialic Acid-specific O-Acetyltransferase NeuO of Escherichia coli K1 J. Biol. Chem., July 27, 2007; 282(30): 22217 - 22227. [Abstract] [Full Text] [PDF]

				J. R. Bishop and P. Gagneux Evolution of carbohydrate antigens--microbial forces shaping host glycomes? Glycobiology, May 1, 2007; 17(5): 23R - 34R. [Abstract] [Full Text] [PDF]

				M. L. Warwas, J. N. Watson, A. J. Bennet, and M. M. Moore Structure and role of sialic acids on the surface of Aspergillus fumigatus conidiospores Glycobiology, April 1, 2007; 17(4): 401 - 410. [Abstract] [Full Text] [PDF]

				A. F. Carlin, A. L. Lewis, A. Varki, and V. Nizet Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes J. Bacteriol., February 15, 2007; 189(4): 1231 - 1237. [Abstract] [Full Text] [PDF]

				S. M. Steenbergen, Y.-C. Lee, W. F. Vann, J. Vionnet, L. F. Wright, and E. R. Vimr Separate Pathways for O Acetylation of Polymeric and Monomeric Sialic Acids and Identification of Sialyl O-Acetyl Esterase in Escherichia coli K1. J. Bacteriol., September 1, 2006; 188(17): 6195 - 6206. [Abstract] [Full Text] [PDF]