heparitin-sulfate and Bacterial-Infections

Syndecan-1 (Sdc1) is a major cell surface heparan sulfate (HS) proteoglycan of epithelial cells, a cell type targeted by many bacterial pathogens early in their pathogenesis. Loss of Sdc1 in mice is a gain-of-function mutation that significantly decreases the susceptibility to several bacterial infections, suggesting that subversion of Sdc1 is an important virulence strategy. HS glycosaminoglycan (GAG) chains of cell surface Sdc1 promote bacterial pathogenesis by facilitating the attachment of bacteria to host cells. Engagement of cell surface Sdc1 HS chains by bacterial adhesins transmits signal through the highly conserved Sdc1 cytoplasmic domain, which can lead to uptake of intracellular bacterial pathogens. On the other hand, several bacteria that do not require Sdc1 for their attachment and invasion stimulate Sdc1 shedding and exploit the capacity of Sdc1 ectodomain HS GAGs to disarm innate defense mechanisms to evade immune clearance. Recent data suggest that select HS sulfate motifs, and not the overall charge of HS, are important in the inhibition of innate immune mechanisms. Here, we discuss several examples of Sdc1 subversion in bacterial infections.

Topics: Adhesins, Bacterial; Animals; Bacterial Infections; Glycomics; Glycosaminoglycans; Heparitin Sulfate; Mice; Mutation; Syndecan-1; Virulence

Heparan sulfate proteoglycans (HSPGs) are at the forefront of host-microbe interactions. Cell surface HSPGs are thought to promote infection as attachment and internalization receptors for many bacterial pathogens and as soluble inhibitors of host immunity when released from the cell surface by ectodomain shedding. However, the importance of HSPG-pathogen interactions in vivo has yet to be clearly established. Here we describe several representative methods to study the role of HSPGs in systemic bacterial infections, such as bacteremia and sepsis. The overall experimental strategy is to use mouse models to establish the physiological significance of HSPGs, to determine the identity of HSPGs that specifically promote infection, and to define key structural features of HSPGs that enhance bacterial virulence in systemic infections.

Topics: Animals; Bacterial Infections; Cell Membrane; Disease Models, Animal; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Mice; Sepsis

The attachment of a variety of

Topics: Bacterial Infections; Bacterial Proteins; Cell Line, Tumor; Chondroitin Sulfates; Glycosaminoglycans; HeLa Cells; Heparitin Sulfate; Humans; Ligands; Ligilactobacillus salivarius; Protein Biosynthesis; Proteoglycans; Transcription, Genetic

Bacterial infections have been postulated as a trigger for variceal bleeding in cirrhotic patients, and impair coagulation evaluated by thrombelastography (TEG). Endogenous heparinoids have been detected after variceal bleeding and during liver transplantation in some cirrhotics using heparinase-modified-TEG.. To assess if bacterial infection is associated with endogenous heparinoids in cirrhotics, thus impairing coagulation.. Native and heparinase-modified-TEG (cleavage of heparin and heparan-sulphate) was performed in 60 cirrhotics (Grade A, 2; B, 30; C, 28): 30 infected [septicaemia, 6 (culture positive); 6 (culture negative); spontaneous bacterial peritonitis, 10; chest infection, 4; others, 4], 30 not infected, and five infected patients without liver diseases, comparing TEG parameters r, alpha, and ma. Eight cirrhotics were studied before and after infection. The diagnosis of presence and type of infection was based on international standard criteria.. A significant heparin effect was found only in infected cirrhotics (28 of 30) with significant changes in r (P=0.0003), alpha (P<0.0001), and ma (P<0.0001), but in none of those not infected. This effect completely reversed in the eight evaluated after resolution of infection. There was no heparin effect in infected non-cirrhotics.. A heparin effect was only found in cirrhotic patients with infection, further confirming that infection significantly modifies coagulation in cirrhotic patients.

Topics: Adult; Bacterial Infections; Blood Coagulation; Female; Gastrointestinal Hemorrhage; Heparin; Heparin Lyase; Heparinoids; Heparitin Sulfate; Hepatitis, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Peritonitis; Thrombelastography

The plasma concentration of biological active fibronectin was assayed by a protein binding assay using 125I-collagen I as ligand and heparin as activator. The standard curve is linear for a fibronectin range of 1.1-11 pmol (0.5-5.0 micrograms) and the coefficient of variation was less than 10%. The active or activable fibronectin was compared to the immunoreactive fibronectin in plasma from patients with various bacterial diseases. Similar concentrations were detected by the two assays suggesting that all the circulating fibronectin was functionally active. The assay was also applied to determine the structure-function relationship of heparin and heparansulphate in activation of fibronectin. Low-sulphated heparansulphate from umbilical cords and heparin-activated fibronectin but the effect was uncorrelated to anticoagulation activity. Only a small fraction of the heparin was actually capable of activating fibronectin. It is concluded that the assay is very convenient to detect biological active fibronectin and to elucidate the structure-function relationship of heparin and heparansulphate in activating fibronectin.

Topics: Adult; Bacterial Infections; Collagen; Female; Fibronectins; Heparin; Heparitin Sulfate; Humans; Iodine Radioisotopes; Isotope Labeling; Male; Middle Aged; Radioligand Assay; Structure-Activity Relationship