Distinct biological activity of lipopolysaccharides with different lipid a acylation status from mutant strains of Yersinia pestis and some members of genus Psychrobacter
Correlation between the chemical structure of lipid A from various Gram-negative bacteria and biological activity of their lipopolysaccharide (LPS) as an agonist of the innate immune receptor Toll-like receptor 4 was investigated. Purified LPS species were quantitatively evaluated by their ability to activate the production of tumor necrosis factor (TNF) by murine bone marrow-derived macrophages in vitro. Wild-type LPS from plague-causing bacteria Yersinia pestis was compared to LPS from mutant strains with defects in acyltransferase genes (lpxM, lpxP) responsible for the attachment of secondary fatty acid residues (12:0 and 16:1) to lipid A. Lipid A of Y. pestis double ΔlpxM/ΔlpxP mutant was found to have the chemical structure that was predicted based on the known functions of the respective acyltransferases. The structures of lipid A from two members of the ancient psychrotrophic bacteria of the genus Psychrobacter were established for the first time, and biological activity of LPS from these bacteria containing lipid A fatty acids with shorter acyl chains (C10–C12) than those in lipid A from LPS of Y. pestis or E. coli (C12–C16) was determined. The data revealed a correlation between the ability of LPS to activate TNF production by bone marrow-derived macrophages with the number and the length of acyl chains within lipid A.
Key wordslipopolysaccharide lipid A Toll-like receptor 4 tumor necrosis factor Yersinia pestis Psychrobacter spp.
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- 1.Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., and Beutler, B. (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene, Science, 282, 2085–2088.PubMedCrossRefGoogle Scholar
- 5.Qureshi, N., Takayama, K., Mascagni, P., Honovich, J., Wong, R., and Cotter, R. J. (1988) Complete structural determination of lipopolysaccharide obtained from deep rough mutant of Escherichia coli. Purification by high performance liquid chromatography and direct analysis by plasma desorption mass spectrometry, J. Biol. Chem., 263, 11971–11976.PubMedGoogle Scholar
- 8.Maeshima, N., and Fernandez, R. C. (2012) Recognition of lipid A variants by the TLR4-MD-2 receptor complex, Front. Cell. Infect. Microbiol., 3, 3.Google Scholar
- 11.Anisimov, A. P., Shaikhutdinova, R. Z., Pan’kina, L. N., Feodorova, V. A., Savostina, E. P., Bystrova, O. V., Lindner, B., Mokrievich, A. N., Bakhteeva, I. V., Titareva, G. M., Dentovskaya, S. V., Kocharova, N. A., Senchenkova, S. N., Holst, O., Devdariani, Z. L., Popov, Y. A., Pier, G. B., and Knirel, Y. A. (2007) Effect of deletion of the lpxM gene on virulence and vaccine potential of Yersinia pestis in mice, J. Med. Microbiol., 56, 443–453.PubMedCrossRefGoogle Scholar
- 12.Dentovskaya, S. V., Anisimov, A. P., Kondakova, A. N., Lindner, B., Bystrova, O. V., Svetoch, T. E., Shaikhutdinova, R. Z., Ivanov, S. A., Bakhteeva, I. V., Titareva, G. M., and Knirel, Y. A. (2011) Functional characterization and biological significance of Yersinia pestis lipopolysaccharide biosynthesis genes, Biochemistry (Moscow), 76, 808–822.CrossRefGoogle Scholar
- 13.Bakermans, C., Ayala-del-Rio, H. L., Ponder, M. A., Vishnivetskaya, T., Gilichinsky, D., Thomashow, M. F., and Tiedje, J. M. (2006) Psychrobacter cryohalolentis sp. nov. and Psychrobacter arcticus sp. nov., isolated from Siberian permafrost, Int. J. Syst. Evol. Microbiol., 56, 1285–1291.PubMedCrossRefGoogle Scholar
- 15.Knirel, Y. A., Lindner, B., Vinogradov, E. V., Kocharova, N. A., Senchenkova, S. N., Shaikhutdinova, R. Z., Dentovskaya, S. V., Fursova, N. K., Bakhteeva, I. V., Titareva, G. M., Balakhonov, S. V., Holst, O., Gremyakova, T. A., Pier, G. B., and Anisimov, A. P. (2005) Temperature-dependent variations and intraspecies diversity of the structure of the lipopolysaccharide of Yersinia pestis, Biochemistry, 44, 1731–1743.PubMedCrossRefGoogle Scholar
- 19.Kondakova, A. N., Novototskaya-Vlasova, K. A., Arbatsky, N. P., Drutskaya, M. S., Shcherbakova, V. A., Shashkov, A. S., Gilichinsky, D. A., Nedospasov, S. A., and Knirel, Y. A. (2012) Structure of the O-specific polysaccharide from the lipopolysaccharide of Psychrobacter cryohalolentis K5T containing a 2,3,4-triacetamido-2,3,4-trideoxy-L-arabinose moiety, J. Nat. Prod., 75, 2236–2240.PubMedCrossRefGoogle Scholar