Distinct Biological Activity of Lipopolysaccharides with Different Lipid A Acylation Status from Mutant Strains of Yersinia pestis and Some Members of Genus Psychrobacter

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K. V. Korneev^1,2,3, A. N. Kondakova⁴, N. P. Arbatsky⁴, K. A. Novototskaya-Vlasova⁵, E. M. Rivkina⁵, A. P. Anisimov⁶, A. A. Kruglov^2,3, D. V. Kuprash^1,2,3, S. A. Nedospasov^1,2,3, Yu. A. Knirel^4*#, and M. S. Drutskaya^1*#

¹Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (499) 135-1405; E-mail: marinadru@gmail.com

²Department of Immunology, Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia

³Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

⁴Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky pr. 47, 119991 Moscow, Russia; fax: (499) 135-5328; E-mail: yknirel@gmail.com

⁵Institute for Physicochemical and Biological Problems in Soil Science, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia; fax: (4967) 33-0532; E-mail: soil@issp.serpukhov.su

⁶State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Moscow Region, Russia; fax: (4967) 36-0010; E-mail: info@obolensk.org

^* To whom correspondence should be addressed.

^# These authors contributed equally to this work.

Received June 30, 2014

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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.

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KEY WORDS: lipopolysaccharide, lipid A, Toll-like receptor 4, tumor necrosis factor, Yersinia pestis, Psychrobacter spp.

DOI: 10.1134/S0006297914120062

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