Bacterial Toxin Requires Dietary Sugar Residues

Bacteriologists have found that the subtilase cytotoxin (SubAB) produced by pathogenic Escherichia coli O157:H7 preferentially binds to cell surface sugar residues that are not produced by humans and must be incorporated from the diet.

E. coli is a normal inhabitant of the intestines of all animals, including humans. Normally E. coli serves a useful function in the body by suppressing the growth of harmful bacterial species and by synthesizing appreciable amounts of vitamins. A minority of E. coli strains is capable of causing human illness by several mechanisms. E. coli serotype O157:H7 is a rare variety that produces large quantities of one or more related, potent toxins that cause severe damage to the lining of the intestine. These toxins (verotoxin, shiga-like toxin) are closely related or identical to the toxin produced by Shigella dysenteriae. Subtilase cytotoxin (SubAB) is an AB5 toxin secreted by Shiga toxigenic E. coli (STEC) that causes serious gastrointestinal disease in humans.

In a recent paper published in the October 29, 2008, issue of the journal Nature investigators at the University of Adelaide (Australia) found that SubAB specifically targeted human cells that expressed sialic acid N-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans, on their surface.

The main sources of Neu5Gc are red meat and dairy products. Therefore, the richest dietary sources of Neu5Gc are also the foods that are most commonly contaminated with the E. coli O157:H7 bacteria that produce the toxin.

SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human-like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite lack of Neu5Gc biosynthesis in humans, assimilation of dietary Neu5Gc created high-affinity receptors on cells from the human gut and kidney.

"Remarkably, humans cannot make Neu5Gc, and so we should all be resistant to the toxin,” said senior author Dr. James Paton, professor of molecular microbiology at the University of Adelaide. "However, consuming foods that have high levels of Neu5Gc, such as red meat and dairy products, leads to uptake of the sugar by human cells and this makes them susceptible to attack by the toxin. Through dietary choices, therefore, humans may expose themselves to an increased risk of infection with the E. coli bacteria and simultaneously sensitize themselves to the potentially lethal actions of the toxin it produces.”

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