Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial adhesion to host receptors is an early and essential step in bacterial colonization, and the nature of adhesin-receptor interactions determines bacterial localization and thus the outcome of these interactions. Here, we determined the host receptors for the multivalent adhesion molecule (MAM) from the gut commensal Escherichia coli HS (MAMHS), which contains an array of seven mammalian cell entry domains. The MAMHS adhesin interacted with a range of host receptors, through recognition of a shared 3-O-sulfogalactosyl moiety. This functional group is also found in mucin, a component of the intestinal mucus layer and thus one of the prime adherence targets for commensal E. coli Mucin gels impeded the motility of E. coli by acting as a physical barrier, and the barrier effect was enhanced by specific interactions between mucin and MAMHS in a sulfation-dependent manner. Desulfation of mucin by pure sulfatase or the sulfatase-producing commensal Bacteroides thetaiotaomicron decreased binding of E. coli to mucin and increased the attachment of bacteria to the epithelial surface via interactions with surface-localized sulfated lipid and protein receptors. Together, our results demonstrate that the E. coli adhesin MAMHS facilitates retention of a gut commensal by attachment to mucin. They further suggest that the amount of sulfatase secreted by mucin-foraging bacteria such as B. thetaiotaomicron, inhabiting the same niche, may affect the capacity of the mucus barrier to retain commensal E. coli.
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PMID:3-Sulfogalactosyl-dependent adhesion of Escherichia coli HS multivalent adhesion molecule is attenuated by sulfatase activity. 2898 77

Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to postseptic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. Seventy-two hours after experimental sepsis, coincident with glycocalyx reconstitution, mice demonstrated impaired neutrophil and protein influx in response to intratracheal lipopolysaccharide (LPS). The postseptic reconstituted glycocalyx was structurally remodeled, with enrichment of heparan sulfate disaccharides sulfated at the 6-O position of glucosamine. Increased 6-O-sulfation coincided with loss of endothelial sulfatase-1 (Sulf-1), an enzyme that specifically removes 6-O-sulfates from heparan sulfate. Intravenous administration of Sulf-1 to postseptic mice restored the pulmonary response to LPS, suggesting that loss of Sulf-1 was necessary for postseptic suppression of pulmonary inflammation. Endothelial-specific knockout mice demonstrated that loss of Sulf-1 was not sufficient to induce immunosuppression in non-septic mice. Knockdown of Sulf-1 in human pulmonary microvascular endothelial cells resulted in downregulation of the adhesion molecule ICAM-1. Taken together, our study indicates that loss of endothelial Sulf-1 is necessary for postseptic suppression of pulmonary inflammation, representing a novel endothelial contributor to CARS.
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PMID:Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses. 3146 25