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Infection and Immunity, December 2008, p. 5777-5789, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00676-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Modification of Lipooligosaccharide with Phosphoethanolamine by LptA in Neisseria meningitidis Enhances Meningococcal Adhesion to Human Endothelial and Epithelial Cells{triangledown}

Hideyuki Takahashi,1* Russel W. Carlson,2 Artur Muszynski,2 Biswa Choudhury,2 Kwang Sik Kim,3 David S. Stephens,4,5,6 and Haruo Watanabe1

Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan,1 University of Georgia, Complex Carbohydrate Research Center, Athens, Georgia,2 Division of Pediatric Infectious Diseases, Department of Pediatrics, School of Medicine, John Hopkins University, Baltimore, Maryland,3 Division of Infectious Diseases, Department of Medicine,4 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia,5 Department of Veterans Affairs Medical Center, Atlanta, Georgia6

Received 30 May 2008/ Returned for modification 10 July 2008/ Accepted 9 September 2008

The lipooligosaccharide (LOS) of Neisseria meningitidis can be decorated with phosphoethanolamine (PEA) at the 4' position of lipid A and at the O-3 and O-6 positions of the inner core of the heptose II residue. The biological role of PEA modification in N. meningitidis remains unclear. During the course of our studies to elucidate the pathogenicity of the ST-2032 (invasive) meningococcal clonal group, disruption of lptA, the gene that encodes the PEA transferase for 4' lipid A, led to a approximately 10-fold decrease in N. meningitidis adhesion to four kinds of human endothelial and epithelial cell lines at an multiplicity of infection of 5,000. Complementation of the lptA gene in a {Delta}lptA mutant restored wild-type adherence. By matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis, PEA was lost from the lipid A of the {Delta}lptA mutant compared to that of the wild-type strain. The effect of LptA on meningococcal adhesion was independent of other adhesins such as pili, Opc, Opa, and PilC but was inhibited by the presence of capsule. These results indicate that modification of LOS with PEA by LptA enhances meningococcal adhesion to human endothelial and epithelial cells in unencapsulated N. meningitidis.

* Corresponding author. Mailing address: Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111. Fax: 81-3-5285-1163. E-mail: hideyuki{at}nih.go.jp

{triangledown} Published ahead of print on 29 September 2008.

Editor: J. N. Weiser

Infection and Immunity, December 2008, p. 5777-5789, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00676-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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