Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence

• Published in: Nature (London) Vol. 411; no. 6833; pp. 98 - 102
• Main Authors: Bernfield, Merton, Park, Pyong Woo, Pier, Gerald B, Hinkes, Michael T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 03.05.2001; Nature Publishing Group
• Subjects: Animals; Animals, Newborn; Bacteria; Bacterial Adhesion; Bacteriology; Biological and medical sciences; Disease Models, Animal; disease resistance; Fundamental and applied biological sciences. Psychology; heparan sulfate proteoglycans; Heparin - pharmacology; Heparitin Sulfate - metabolism; Infections; LasA protein; Lung - metabolism; Lung - microbiology; Lung Diseases - metabolism; Lung Diseases - microbiology; Lungs; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - physiology; Mice; Mice, Inbred BALB C; Microbiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Protein Structure, Tertiary; Proteoglycans - chemistry; Proteoglycans - physiology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Rodents; Syndecan-1; Syndecans; Virulence; Pseudomonadales; Proteoglycan; Animal model; Lung; Rodentia; Host agent relation; Syndecan 1; Respiratory system; Cell surface; Infection; Pathogenicity; Vertebrata; Experimental disease; Mammalia; Mouse; Newborn animal; Bacteriosis; Bacteria; Pseudomonadaceae; Epithelial cell; Heparitin sulfate; Pseudomonas aeruginosa; Colonization; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35075100

Cell-surface heparan sulphate proteoglycans (HSPGs) are ubiquitous and abundant receptors/co-receptors of extracellular ligands, including many microbes. Their role in microbial infections is poorly defined, however, because no cell-surface HSPG has been clearly connected to the pathogenesis of a particular microbe. We have previously shown that Pseudomonas aeruginosa, through its virulence factor LasA, enhances the in vitro shedding of syndecan-1-the predominant cell-surface HSPG of epithelia. Here we show that shedding of syndecan-1 is also activated by P. aeruginosa in vivo, and that the resulting syndecan-1 ectodomains enhance bacterial virulence in newborn mice. Newborn mice deficient in syndecan-1 resist P. aeruginosa lung infection but become susceptible when given purified syndecan-1 ectodomains or heparin, but not when given ectodomain core protein, indicating that the ectodomain's heparan sulphate chains are the effectors. In wild-type newborn mice, inhibition of syndecan-1 shedding or inactivation of the shed ectodomain's heparan sulphate chains prevents lung infection. Our findings uncover a pathogenetic mechanism in which a host response to tissue injury-syndecan-1 shedding-is exploited to enhance microbial virulence apparently by modulating host defences.