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Journal of Bacteriology, April 2008, p. 2379-2387, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01795-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A New Model of Pneumococcal Lipoteichoic Acid Structure Resolves Biochemical, Biosynthetic, and Serologic Inconsistencies of the Current Model{triangledown}

Ho Seong Seo,1,2 Robert T. Cartee,2 David G. Pritchard,3 and Moon H. Nahm1,2*

Departments of Pathology,1 Microbiology,2 Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 352943

Received 13 November 2007/ Accepted 18 January 2008

Lipoteichoic acid (LTA) is an essential bacterial membrane polysaccharide (cell wall component) that is attached to the membrane via a lipid anchor. According to the currently accepted structure of pneumococcal LTA, the polysaccharide is comprised of several repeating units, each of which starts with glucose and ends with ribitol, with the lipid anchor predicted to be Glc(β1->3)AATGal(β1->3)Glc({alpha}1->3)-acyl2Gro, where AATGal is 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose. However, this lipid anchor has not been detected in pneumococcal membranes. Furthermore, the currently accepted structure does not explain the Forssman antigen properties of LTA and predicts a molecular weight for LTA that is larger than its actual observed molecular weight. To resolve these problems, we used mass spectrometry to analyze the structure of LTA isolated from several pneumococcal strains. Our study found that the R36A pneumococcal strain produces LTA that is more representative of pneumococci than that previously characterized from the R6 strain. Analysis of LTA fragments obtained after hydrofluoric acid and nitrous treatments showed that the fragments were consistent with an LTA nonreducing terminus consisting of GalNAc({alpha}1->3)GalNAc(β1->, which is the minimal structure for the Forssman antigen. Based on these data, we propose a revised model of LTA structure: its polysaccharide repeating unit begins with GalNAc and ends with AATGal, and its lipid anchor is Glc({alpha}1->3)-acyl2Gro, a common lipid anchor found in pneumococcal membranes. This new model accurately predicts the observed molecular weights. The revised model should facilitate investigation of the relationship between LTA's structure and its function.

* Corresponding author. Mailing address: Department of Pathology, University of Alabama at Birmingham, 845 19th Street South (BBRB-614), Birmingham, AL 35294. Phone: (205) 934-0163. Fax: (205) 975-2149. E-mail: nahm{at}UAB.edu

{triangledown} Published ahead of print on 1 February 2008.

Journal of Bacteriology, April 2008, p. 2379-2387, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01795-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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