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Infection and Immunity, May 2007, p. 2253-2259, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.00141-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Synthesis and Characterization of a Dipalmitoylated Lipopeptide Derived from Paralogous Lipoproteins of Mycoplasma pneumoniae ^,

Takeshi Into,^1,* Jun-ichi Dohkan,^1, Megumi Inomata,¹ Misako Nakashima,¹ Ken-ichiro Shibata,² and Kenji Matsushita¹

Department of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan,¹ Laboratory of Oral Molecular Microbiology, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan²

Received 28 January 2007/ Accepted 12 February 2007

Genomic analysis of Mycoplasma pneumoniae revealed the existence of a large number of putative lipoprotein genes compared with the numbers in other bacteria. However, the pathogenic roles of M. pneumoniae lipoproteins are still obscure. In this study, we synthesized a lipopeptide (designated M. pneumoniae paralogous lipoprotein 1 [MPPL-1]) in which an S-dipalmitoylglyceryl cysteine was coupled to a peptide with a consensus sequence of a putative paralogous lipoprotein group characteristic of M. pneumoniae. The cytokine-inducing activity of MPPL-1 in human monocytic cells was much weaker (700-fold weaker) than that of the known mycoplasmal S-dipalmitoylated lipopeptide FSL-1 or MALP-2. MPPL-1 required Toll-like receptor (TLR2) to activate NF-B-dependent gene transcription in HEK293 cells, although a 1,000-fold-larger amount of MPPL-1 was needed to exert activity similar to that of FSL-1 in the cells. TLR2-mediated recognition of MPPL-1 was synergistically upregulated by TLR6 but not by TLR1 or TLR10, although the activity was still weak. In addition, MPPL-1 did not antagonize FSL-1 recognition in human monocytic cells and TLR2/TLR6-expressing HEK293 cells. Thus, these results suggest that there is preferential selective recognition of diacylated lipopeptides due to the magnitude of an affinity with TLR2 and TLR6 and the roles of increased paralogous lipoprotein genes of M. pneumoniae in evasion of TLR2 recognition.

Published ahead of print on 26 February 2007.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: D. L. Burns

T.I. and J.D. contributed equally to this work.

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