Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence

Pyong Woo Park, Gerald B. Pier, Michael T. Hinkes and Merton Bernfield ()
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Pyong Woo Park: Children's Hospital and
Gerald B. Pier: Harvard Medical School
Michael T. Hinkes: Children's Hospital and
Merton Bernfield: Children's Hospital and

Nature, 2001, vol. 411, issue 6833, 98-102

Abstract: Abstract Cell-surface heparan sulphate proteoglycans (HSPGs) are ubiquitous and abundant receptors/co-receptors of extracellular ligands1,2, including many microbes3,4,5,6,7,8,9,10. 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 epithelia11. 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.

Date: 2001
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DOI: 10.1038/35075100

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