title: Synthesis and characterization of a dipalmitoylated lipopeptide derived from paralogous lipoproteins of Mycoplasma pneumoniae.
abstract: 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 (approximately 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-kappaB-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.
authors.affiliation: Department of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu, Aichi 474-8522, Japan. into@nils.go.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Into
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Dohkan
authors.forename: Megumi
authors.initials: M
authors.lastname: Inomata
authors.forename: Misako
authors.initials: M
authors.lastname: Nakashima
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Shibata
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004075:Diglycerides / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D008262:Macrophage Activation; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009177:Mycoplasma pneumoniae / Q000737:chemistry* / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D019308:Palmitic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D055666:Lipopeptides; D008074:Lipoproteins; D009842:Oligopeptides; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D019308:Palmitic Acid; C106335:macrophage stimulatory lipopeptide 2