Influence of lipoteichoic acid structure on recognition by the macrophage scavenger receptor.

Infection and Immunity
J GreenbergK A Joiner

Abstract

Lipoteichoic acids (LTAs) belong to the immunostimulatory class of molecules of gram-positive bacteria (GPB). Previous investigations showed that the macrophage scavenger receptor (SR), a glycosylated trimeric transmembrane protein, binds directly to many GPB, possibly via LTA. SR binding to other ligands is dependent upon the spatial characteristics of the repeating negative charge of the ligand. We therefore investigated SR recognition of LTA species with various charge densities and distributions by determining the capacity of these LTAs to compete with the binding of metabolically labeled SR to beads coated with the known SR ligand polyguanylic acid. Staphylococcus aureus LTA, a classical LTA type (unbranched 1,3-linked polyglycerophosphate chain covalently bound to a membrane diacylglyceroglycolipid), had a 50% inhibitory concentration (IC50) for inhibition of SR binding of 0.84 microg/ml. When the S. aureus LTA was rendered more negatively charged by removal of ester-linked alanine from the polyglycerophosphate backbone, the IC50 dropped to 0.23 microg/ml. Other polyglycerophosphate LTAs from Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Listeria monocytogenes, Listeria welshimeri, and Streptococcus san...Continue Reading

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