Divalent cations affect chain mobility and aggregate structure of lipopolysaccharide from Salmonella minnesota reflected in a decrease of its biological activity

Abstract

The physicochemical properties and biological activities of rough mutant lipopolysaccharides Re (LPS Re) as preformed divalent cation (Mg2+, Ca2+, Ba2+) salt form or as natural or triethylamine (Ten+)-salt form under the influence of externally added divalent cations were investigated using complementary methods: Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopic (FT-IR) measurements for the beta <--> alpha gel to liquid crystalline phase behaviour of the acyl chains of LPS, synchrotron radiation X-ray diffraction studies for their aggregate structures, electron density calculations of the LPS bilayer systems, and LPS-induced cytokine (interleukin-6) production in human mononuclear cells. The divalent cation salt forms of LPS exhibit considerable changes in physicochemical parameters such as acyl chain mobility and aggregate structures as compared to the natural or monovalent cation salt forms. Concomitantly, the biological activity was much lower in particular for the Ca2+- and Ba2+-salt forms. This decrease in activity results mainly from the conversion of the unilamellar/cubic aggregate structure of LPS into a multilamellar one. The reduced activity also clearly correlates with the higher order--lower mobility--of the lipid A acyl chains. Both effects can be understood by an impediment of the interactions of LPS with binding proteins such as lipopolysaccharide-binding protein (LBP) and CD14 due to the action of the divalent cations.

Phosphorylcholine Allows for Evasion of Bactericidal Antibody by Haemophilus influenzae

“…A similar trend is observed in phospholipid membrane systems, where the addition of lipids containing ChoP reduce membrane permeability and the T m [47]. In DSC experiments using LPS isolated from Salmonella minnesota , it was found that mutants with reduced oligosaccharide extensions had a lower T m , demonstrating that changes to the oligosaccharide, in addition to lipid A alterations, can affect the phase transition temperature [51], [73].…”

“…Increasing the Mg 2+ concentration (up to 50 mM) resulted in reduced antibody binding to the ChoP− phase variant of H233 (Figure 8E). These results demonstrate that excess Mg 2+ , which increases the stability of the outer membrane [49]–[51], can correct for the difference in antibody binding between ChoP+ and ChoP− variants. Together, these data indicate that ChoP expression alters the physical properties of the outer membrane, and that these effects correlate with the reduction of antibody binding in ChoP+ phase variants.…”

Effects of the nonsteroidal anti-inflammatory drug naproxen on human erythrocytes and on cell membrane molecular models

“…The DSC data were analyzed using the Origin software. The phase transition enthalpy was obtained by integrating the area under the heat capacity curve [16].…”

Nutrition, microbiota, and endotoxin-related diseases in dairy cows

“…Indeed, Waldron et al (2003) reported that experimental endotoxemia was associated with hypocalcemia. It is not clear whether lowering of plasma calcium occurs because calcium binds endotoxin to neutralize its biological effects as suggested by Garidel et al (2005) or because calcium mobilization is impaired during administration of endotoxin (Zaloga et al, 1992). This remains to be clarified in the future.…”