Novel inhibitors targeting colonization and virulence of gastrointestinal pathogens
Diseases caused by toxin-producing pathogens are a worldwide health threat. Shiga Toxin (Stx)-producing Escherichia coli (STEC) and in particular human pathogenic enterohemorrhagic E. coli (EHEC) cause severe intestinal infections such as hemorrhagic colitis and lifeendangering extraintestinal complications like the hemolytic-uremic syndrome (HUS). Stx, by definition a lectin with certain carbohydratebinding specificity, belongs to the group of AB5 toxins and represents the major virulence factor of EHEC. So far, no causal treatment of EHEC infections is available. The lack of causal therapy options became evident during large EHEC outbreaks in the past, which were caused by EHEC O157:H7 and O104:H4 serotypes.
The present technology relates to methods of preparing a number of pectic oligosaccharides (POS) and neoglycolipids (neoGLs) that have the potential to inhibit binding of Stx to its genuine receptors on the cell surface of a human or animal.
Besides treatment of EHEC-caused intestinal diseases and extraintestinal or systemic complications, UPEC (uropathogenic E. coli)-triggered urinary tract infections and the edema disease of pigs provide further clinical applications of the produced POS and neoGLs as well.
In addition, there are numerous other implementations to benefit from inhibitory effects of POS and POS-derivatives against toxins re-leased by bacteria into the environment and for adhesin-bearing pathogens in numerous biological habitats. Such compounds might be useful for example as biological adsorbers of toxins or bacteria in filter systems for drinking water purification, swimming pools or spas, for municipal wastewater treatment and for detox-ification of feces in slaughterhouses as well as for air filters of all kinds. Further applications are easily conceivable wherever bacteria-released toxins or adhesive pathogenic bacteria occur.
Advantages of the technology:
- low price of the raw material
- available virtually in unlimited amounts
- nonhazardous for humans and animals
- high "consumer acceptance"