Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment.

Abstract

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal [570][571][572][573][574][575][576]

Sulfatases and a Radical S-Adenosyl-l-methionine (AdoMet) Enzyme Are Key for Mucosal Foraging and Fitness of the Prominent Human Gut Symbiont, Bacteroides thetaiotaomicron

“…This organism, by virtue of its ability to forage sulfated glycans is, in turn, in a position to shape features of its gut habitat, notably modification of host mucins that it likely contacts directly during growth in the mucus layer. Alterations in mucus composition, notably extensive desulfation has been reported in the intestines of individuals with inflammatory bowel diseases (24). As metagenomic studies of the gut microbiomes of individuals with various forms of inflammatory bowel diseases, or other disorders where intestinal mucosal barrier function is disrupted, it will be interesting to ascertain whether the representation and expression of genes encoding sulfatases and the enzymes responsible for their activation correlates with disease type, disease activity, and nutritional status.…”

“…In MM-glucose, as in complex rich BHI medium, both strains exhibited no significant differences in lag time, exponential growth rate, or growth level (Figs. 1B and 3A) (23,24). In contrast, the ⌬anSME strain had a growth defect reaching levels that were 30% of those attained by the wild-type strain in MM porcine mucin and had an average doubling time during log phase growth that was longer than for the wild-type strain (105 versus 84 min; Fig.…”

Desulfurization of mucin by Pseudomonas aeruginosa: influence of sulfate in the lungs of cystic fibrosis patients

“…One notable change in lung secretions is the increased sulfation level that has been reported for mucins in the sputum of CF patients (Boat et al, 1976a;Chace et al, 1983;Davril et al, 1999;Xia et al, 2005). A positive correlation has been suggested between the level of sputum sulfation and the severity of disease in CF patients (Chace et al, 1983) and increased glycan sulfation has been proposed to occur as a response to bacterial infection, possibly to protect the underlying glycoprotein from enzymic degradation by bacteria (Corfield et al, 1993;Tsai et al, 1992Tsai et al, , 1995. This theory has been difficult to study due to the very high rate of bacterial infection in CF patients but mucin oligosaccharides are more resistant to degradation and utilization by P. aeruginosa when sulfated (Chance & Mawhinney, 2000) and mucin in bronchoalveolar lavage (BAL) samples from artificially ventilated patients with ventilator-associated pneumonia has a fivefold higher sulfation level than mucin from artificially ventilated patients without pneumonia (Dennesen et al, 2003).…”

Cloning of a Mucin-Desulfating Sulfatase Gene from Prevotella Strain RS2 and Its Expression Using a Bacteroides Recombinant System

“…Heavily sulfated mucins (sulfomucins) have many of the general lubricating and barrier functions of mucins with lower sulfate levels. There is accumulating evidence that sulfomucins may, in addition, rate-limit mucin degradation by mucin-degrading bacterial enzymes (4,7,13,15,18,24,26,27), and this role is thought to be particularly important in the colon, where approximately 10 14 bacterial cells are located (10). There have been reports of mucin-desulfating sulfatases that partially remove the sulfate from sulfomucin in a number of bacteria from the mouth, stomach, and colon and in feces.…”

“…The effect of such sulfatases is to increase the susceptibility of the mucin to degradation by other mucin-degrading enzymes (4,27). Elevated levels of bacterial mucin-desulfating sulfatases are found in feces of patients with ulcerative colitis (26). The sulfated sugar specificity of these fecal sulfatases, the number of different types present, the bacterial origin of the elevated levels, and the conditions which regulate bacterial production of such enzymes are unknown.…”