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

• Published in: Infection and Immunity Vol. 75; no. 5; pp. 2253 - 2259
• Main Authors: Into, Takeshi, Dohkan, Jun-ichi, Inomata, Megumi, Nakashima, Misako, Shibata, Ken-ichiro, Matsushita, Kenji
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.05.2007
• Subjects: Amino Acid Sequence; Bacteriology; Biological and medical sciences; Cell Line; Cytokines - metabolism; Diglycerides - immunology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Host Response and Inflammation; Humans; Lipopeptides; Lipoproteins - chemical synthesis; Lipoproteins - chemistry; Lipoproteins - immunology; Macrophage Activation; Microbiology; Miscellaneous; Molecular Sequence Data; Monocytes - immunology; Mycoplasma pneumoniae; Mycoplasma pneumoniae - chemistry; Mycoplasma pneumoniae - immunology; Oligopeptides - immunology; Palmitic Acid - chemical synthesis; Palmitic Acid - chemistry; Palmitic Acid - immunology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptors - metabolism; Mollicutes; Mycoplasmatales; Microbiology; Mycoplasma pneumoniae; Bacteria; Lipoprotein; Immunity; Mycoplasmataceae
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00141-07

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-κB-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.