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J. Biol. Chem., Vol. 281, Issue 29, 19939-19948, July 21, 2006

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O-Acetylation of the Terminal N-Acetylglucosamine of the Lipooligosaccharide Inner Core in Neisseria meningitidis

INFLUENCE ON INNER CORE STRUCTURE AND ASSEMBLY^*

Charlene M. Kahler¹, Shauna Lyons-Schindler, Biswa Choudhury, John Glushka, Russell W. Carlson, and David S. Stephens^¶||

From the Department of Microbiology, Monash University, Wellington Road, Victoria 3800, Australia, the Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, and the Departments of ^¶Medicine and ^||Microbiology and Immunology and Laboratories of Microbial Pathogenesis, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia 30322

O-Acetylation is a common decoration on endotoxins derived from many Gram-negative bacterial species, and it has been shown to be instrumental (e.g. in Salmonella typhimurium) in determining the final tertiary structure of the endotoxin and the immunogenicity of the molecule. Structural heterogeneity of endotoxins produced by mucosal pathogens such as Neisseria meningitidis is determined by decorations on the heptose inner core, including O-acetylation of the terminal N-acetylglucosamine (GlcNAc) attached to HepII. In this report, we show that O-acetylation of the meningococcal lipooligosaccharide (LOS) inner core has an important role in determining inner core assembly and immunotype expression. The gene encoding the LOS O-acetyltransferase, lot3, was identified by homology to NodX from Rhizobium leguminosarum. Inactivation of lot3 in strain NMB resulted in the loss of the O-acetyl group located at the C-3 position of the terminal GlcNAc of the LOS inner core. Inactivation of either lot3 or lgtG, which encodes the HepII glucosyltransferase, did not result in the appearance of the O-3-linked phosphoethanolamine (PEA) groups on the LOS inner core. Construction of a double mutant in which both lot3 and lgtG were inactivated resulted in the appearance of O-3-linked PEA groups on the LOS inner core. In conclusion, O-acetylation status of the terminal GlcNAc of the -chain of the meningococcal LOS inner core is an important determinant for the appearance or exclusion of the O-3-linked PEA group on the LOS inner core and contributes to LOS structural diversity. O-Acetylation also likely influences resistance to complement-mediated lysis and may be important in LOS conjugate vaccine design.

Received for publication, February 10, 2006 , and in revised form, May 8, 2006.

^* This work was supported by United States Public Health Services Grant R01 AI033517 from the National Institutes of Health (to D. S. S. and C. M. K.). 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 To whom correspondence should be addressed (present address): School of Biomedical, Biochemical and Chemical Sciences, Discipline of Microbiology and Immunology, L Block QE II Medical Center, Monash Ave., Nedlands, Perth, Western Australia 6009, Australia. Tel.: 61-8-9346-2058; Fax: 61-8-9346-4519; E-mail: ckahler{at}cyllene.uwa.edu.au.

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