Glycosaminoglycan-binding microbial proteins in tissue adhesion and invasion: key events in microbial pathogenicity

Glycosaminoglycans such as heparin, heparan sulphate and dermatan sulphate, are distributed widely in the human body. Several glycosaminoglycans form part of the extracellular matrix and heparan sulphate is expressed on ail e ukaryotic surfaces. The identification of specific binding to different gly cosaminoglycan molecules by bacteria (e.g., Helicobacter pylori, Bordetella pertussis and Chlamydia trachomatis), viruses (e.g., herpes simpler and de ngue virus), and protozoa (e.g., Plasmodium and Leishmania), is therefore o f great interest. Expression of glycosaminoglycan-binding proteins depends on growth and culture conditions in bacteria, and differs in various phases of parasite development. Glycosaminoglycan-binding microbial proteins may mediate adhesion of microbes to eukaryotic cells, which may be a primary me chanism in mucosal infections, and are also involved in secondary effects s uch as adhesion to cerebral endothelia in cerebral malaria or to synovial m embranes in arthritis caused by Borrelia burgdorferi. It has been suggested that they may enhance intracellular survival in macrophages. Microbial bin ding of heparin may interfere with heparin-dependent growth factors, Whethe r or not glycosaminoglycan-binding proteins mediate invasion of epithelial cells is a matter of controversy. Heparin and other glycosaminoglycans may have potential uses as therapeutic agents in microbial infections and could form part of future vaccines against such infections.