Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis.
Fundamental to the virulence of microbial pathogens is their capacity for adaptation and survival within variable, and often hostile, environments encountered in the host. We describe a novel, extragenomic mechanism of surface modulation which may amplify the adaptive and pathogenic potential of numerous bacterial species, including Staphylococcus, Yersinia, and pathogenic Neisseria species, as well as Helicobacter pylori and Streptococcus pyogenes. The mechanism involves specific bacterial recruitment of heparin, glycosaminoglycans, or related sulfated polysaccharides, which in turn serve as universal binding sites for a diverse array of mammalian heparin binding proteins, including adhesive glycoproteins (vitronectin and fibronectin), inflammatory (MCP-3, PF-4, and MIP-1alpha) and immunomodulatory (gamma interferon) intermediates, and fibroblast growth factor. This strategy impacts key aspects of microbial pathogenicity as exemplified by increased bacterial invasion of epithelial cells and inhibition of chemokine-induced chemotaxis. Our findings illustrate a previously unrecognized form of parasitism that complements classical virulence strategies encoded within the microbial genome.
Duensing
T D
TD
Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Wing
J S
JS
van Putten
J P
JP
D000818:Animals; D001419:Bacteria / Q000378:metabolism / Q000472:pathogenicity*; D018407:Bacterial Physiological Phenomena; D016466:CHO Cells; D002461:Cell Line, Transformed; D006224:Cricetinae; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008322:Mammals; D009344:Neisseria gonorrhoeae / Q000378:metabolism / Q000472:pathogenicity; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism; D013210:Staphylococcus / Q000378:metabolism / Q000472:pathogenicity; D013297:Streptococcus pyogenes / Q000378:metabolism / Q000472:pathogenicity; D013431:Sulfates; D019096:Vitronectin / Q000378:metabolism; D015007:Yersinia / Q000378:metabolism / Q000472:pathogenicity
D006497:Heparan Sulfate; D011135:Polysaccharides, Bacterial; D011506:Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D013431:Sulfates; D019096:Vitronectin; C515300:CCR1 protein, human