Structural diversity and endotoxic activity of the lipopolysaccharide of Yersinia pestis

Abstract

The endotoxic activity of the lipopolysaccharides (LPS) with defined chemical structure from Yersinia pestis strains of various subspecies differing in their epidemic potential was studied. The LPS of two strains of Y. pestis ssp. caucasica and ssp. altaica, whose structures have not been studied earlier, were analyzed by high-resolution mass spectrometry. In addition to reported structural changes, an increase in the degree of LPS phosphorylation was observed when strain I-2377 (ssp. altaica) was cultivated at an elevated temperature. A high tumor necrosis factor alpha(TNF-alpha)-inducing activity observed for LPS samples from Y. pestis cultures grown at 25 degrees C correlated with an increased degree of lipid A acylation, particularly, with the presence of the hexaacyl form of lipid A, which was absent from the LPS when bacteria were cultivated at 37 degrees C. No correlation was found between the lethal toxicity of the LPS in vivo and its ability to induce TNF-alpha production in vitro.

Identification of the Lipopolysaccharide Core of Yersinia pestis and Yersinia pseudotuberculosis as the Receptor for Bacteriophage φA1122

“…The main core structure is heptasaccharide, which contains hexoses (Glc (24). In this work, we present conclusive evidence demonstrating that the A1122 receptor is the Hep/Glc-Kdo/Ko region of Y. pestis and Y. pseudotuberculosis LPS.…”

Temperature-Induced Changes in the Lipopolysaccharide ofYersinia pestisAffect Plasminogen Activation by the Pla Surface Protease

“…We compared reactivation of His 6 -Pla by several LPS species which differ in these aspects. The structures of the E. coli and Y. pestis LPSs used here have been determined previously (15,26,31,49,69) (Table 2). Natural LPS molecules are intrinsically heterogeneous in structure and molecular mass due to, e.g., different oligosaccharide chain lengths and the acylation and substitution levels.…”

“…The LPS preparations. The structures of the LPSs isolated from Y. pestis strains KM218, EV11M, and 1146 have been determined previously (15,31,69). The Y. pestis LPSs had been extracted from dried cells with phenol-chloroformlight petroleum ether (19), enzymatically digested first with nucleases and then with proteases, and further purified by ultracentrifugation.…”

“…The adaptation to higher growth temperature is associated with modification of LPS into a tetra-acylated form which has low immunostimulatory activity (15,29,30,55). Biological activities of LPSs are determined by the shape of their hydrophobic lipid A portions, which, on the other hand, are strongly dependent on the acylation and on the charge of endotoxin (57,58).…”

“…A Y. pestis strain genetically modified to express hexa-acylated lipid A only was avirulent in a mouse bubonic plague model (48), indicating that evasion of the LPS-induced inflammatory response is critical for virulence of Y. pestis. Temperature also affects other structural properties of LPS, i.e., the level of substitution in lipid A phosphates and the fine structure of the core oligosaccharide (15,30,31,32). Cavanaugh (11) and McDonough and Falkow (47) reported that the fibrinolytic activity of Y. pestis is dependent on bacterial growth temperature and is enhanced in cells grown at 37°C.…”