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The Journal of Immunology, 2006, 177: 3162-3169.
Copyright © 2006 by The American Association of Immunologists, Inc.

Not Lipoteichoic Acid but Lipoproteins Appear to Be the Dominant Immunobiologically Active Compounds in Staphylococcus aureus1

Masahito Hashimoto2,*, Kazuki Tawaratsumida*, Hiroyuki Kariya*, Ai Kiyohara*, Yasuo Suda*, Fumiko Krikae{dagger}, Teruo Kirikae{dagger} and Friedrich Götz{ddagger}

* Department of Nanostructure and Advanced Materials, Kagoshima University, Kagoshima, Japan; {dagger} Department of Infectious Diseases, International Medical Center of Japan, Tokyo, Japan; and {ddagger} Mikrobielle Genetik, Universität Tübingen, Tübingen, Germany

Lipoteichoic acid (LTA) derived from Staphylococcus aureus is reported to be a ligand of TLR2. However, we previously demonstrated that LTA fraction prepared from bacterial cells contains lipoproteins, which activate cells via TLR2. In this study, we investigated the immunobiological activity of LTA fraction obtained from S. aureus wild-type strain, lipoprotein diacylglycerol transferase deletion ({Delta}lgt) mutant, which lacks palmitate-labeled lipoproteins, and its complemented strain and evaluated the activity of LTA molecule. LTA fraction was prepared by butanol extraction of the bacteria followed by hydrophobic interaction chromatography. Although all LTA fractions activated cells through TLR2, the LTA from {Delta}lgt mutant was 100-fold less potent than those of wild-type and complemented strains. However, no significant structural difference in LTA was observed in NMR spectra. Further, alanylation of LTA molecule showed no effect in immunobiological activity. These results showed that not LTA molecule but lipoproteins are dominant immunobiologically active TLR2 ligand in S. aureus.

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 This work was supported in part by Grants-in-Aid for Encouragement of Young Scientists (B) (16710160) from the Ministry of Education, Culture, Sports, Science and Technology and for Scientific Research (C) (17510179) from the Japanese Society of the Promotion of Science.

2 Address correspondence and reprint requests to Dr. Masahito Hashimoto, Department of Nanostructure and Advanced Materials, Kagoshima University, Korimoto 1-21-40, Kagoshima 890-0065, Japan. E-mail address: hassy{at}eng.kagoshima-u.ac.jp

3 Abbreviations used in this paper: LTA, lipoteichoic acid; AB, alcian blue; BuOH, 1-butanol; HF, hydrofluoric acid; NMR, nuclear magnetic resonance; PEC, peritoneal exudate cell; PrOH, 1-propanol; TX-114, Triton X-114; WT, wild type.




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