Biomedical Engineering Reference
In-Depth Information
The most conserved component in lipopolysaccharides (LPS) from gram-negative
bacteria is lipid A. Lipid A is linked to a core of oligopolysaccharides (Raetz and
Whitefield, 2002), and in its di-phosphorylated form consists of a b-1,6-linked D-
glucosamine disaccharide carrying six saturated fatty-acid residues and two negatively
charged phosphates at the reducing and non-reducing end of the glucosamine (Figure
1). Approximately 1,00,000 patients die in the United States every year from infec-
tions acquired while in the hospital or nursing homes due to the presence of LPS from
gram-negative bacteria. The lipophilic part of LPS, lipid A-diphosphate is associated
with lethal endotoxicity, pyrogenicity, specific immune response. It is also responsible
for triggering a cascade of cellular mediators, for example tumor necrosis factor (TNF)
α, interleukins, leukotrienes, thromboxane A2 from monocytes
and macrophages. A
detailed insight into the spatial-structure and the packing of toxic and non-toxic lipid
A phosphates will aid in the understanding of the following: self-assembly, physi-
cal interactions with gram-negative bacteria, biofilm associations, LPS components,
antibiotic resistance, membrane components, cationic antimicrobial (CAM) peptides,
membrane fusion, and divalent cations, particularly Mg
2+
and Ca
2+
ions (Ernst et al.,
1999; Faunce et al., 2005). From specular neutron scattering studies it is observed
that these divalent counterions modulate the mechanical properties of interacting LPS
membranes (Schneck et al., 2009).
Figure 1.
Chemical structures of lipid A-diphosphate (
a
) and two antagonistic lipid A-diphosphate
molecules, (B and C). Lipid A-diphosphate from
E. coli
is a 1,4-di-phosphorylated
b
-1,6-linked
D-glucosamine disaccharide with four residues of amide-and esterified R-(-)-3-hydroxy fatty acids (
*
denotes the chiral centers in the hydroxy fatty-acid esters, apart form the chiral and epimeric carbons
in the disaccharide moieties which are not marked). The antagonistic lipid A-diphosphate molecules
shown in (B) and (C)
contain the same disaccharide as in (A); however, they differ in the number
anchored carbohydrate positions and the number of chiral fatty-acid chains but the chain lengths is
the same (C
14
). The corresponding monophosphate of lipid A is only phosphorylated at the reducing
end of the disaccharide.
Until recently the self-organization of charged particles, like lipid A-diphosphate,
its analogues and their effects on complex fluids received little attention. In addition,
charged particle dispersions in nano-size the regime such as lipid A-diphosphate can
influence the stability of the system. This is a result of a segregation of domains near
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