This news release is also available in French and Swedish.
A spoonful of sugar may help the medicine go down, but for the 50 percent of the global population whose stomachs contain the Helicobacter pylori bacteria, other sugars have less sweet implications. Certain sugars in the body, meant to help the immune system fight the infection (which can lead to ulcers and stomach cancer), actually make the infection worse, according to a report in the journal Science, published by the American Association for the Advancement of Science.
These findings, by a team of Swedish, Estonian, French, and U.S. researchers, help explain why H. pylori is such a tenacious, virulent bug, and provide new prospects for making a vaccine against it.
There are many different strains of H. pylori, some more harmful than others. They cause virtually all ulcers (spicy food and stress do not) and have been linked to stomach cancer, one of the five most common types of cancer in the world, according to the World Health Organization.
H. pylori infections are far more common in the developing world than they are in North America and Europe, said study author Thomas Borén of Umeå University, in Umeå, Sweden. He noted that, while ulcers can be treated with antibiotics, using this type of treatment globally would likely lead to the emergence of drug resistant bacterial strains.
"I think the real therapeutic strategy would be a vaccine," Borén said.
During an H. pylori infection, when the bacteria are burrowing into the mucus membrane lining the stomach, the membrane cells display certain sugar molecules on their surfaces. The sugars help usher immune cells into the damaged tissue, but they have an unintended consequence as well, Borén and his colleagues found.
H. pylori use the same molecules to fasten themselves securely to the stomach walls, using special "adhesin" proteins that bind with the sugars, researchers report. Thus, the bacteria can co-opt the body's defense system for their own hostile purposes.
"The bacteria are exceedingly adaptive," Borén said.
Interestingly, the two adhesins discovered thus far belong to a group of proteins that seem to be unique to H. pylori.
"The bacteria's ancestor seems to have come up with these proteins all by itself," Borén said.
This uniqueness bodes well for a vaccine "cocktail" of adhesin proteins, since a common obstacle to vaccines is that they aren't specific enough to be effective, Borén explained.
Borén and other researchers had previously identified another adhesin protein, called "BabA," on H. pylori's surface, that binds to the sugar molecule "Leb."
To investigate whether the bacteria used other adhesins for similar purposes, the Science authors generated a mutant form of the bacteria lacking the BabA gene. They named the sugar to which it bound, "sdiLex."
Using biopsies from humans and a rhesus monkey, the researchers found that the mutant bacteria were binding to mucus membrane cells of infected individuals, and not those of healthy individuals. The membrane cells seemed to be "shooting themselves in the foot," so to speak, by displaying more sugars once they were under siege by H. pylori.
With the assistance of the sequenced H. pylori genome, the researchers identified the gene encoding the bacterial adhesin protein, which they called "SabA" (for Sialic acid binding Adhesin).
The other authors of the study are Jafar Mahdavi, Berit Sondén, Marina Hurtig, Farzad O. Olfat, Lina Forsberg, Anna Arnqvist, and Bertil B. Lundskog, of Umeå U., in Umeå, Sweden; Farzad O. Olfat is also at the Swedish Institute for Infectious Disease Control, in Solna, Sweden; Berit Sondén is also at Institute Pasteur, in Paris, France; Niamh Roche, Jonas Ångström, Thomas Larsson, Susann Teneberg, and Karl-Anders Karlsson, at Göteborg U., in Göteborg, Sweden; Siiri Altraja at Tartu U., in Tartu, Estonia; Torkel Wadström, at Lund U., in Lund, Sweden; Dangeruta Kersulyte, and Douglas E. Berg, at Washington U. Medical School, in St. Louis, MO; Andre Dubois at USUHS in Bethesda, MD; Christoffer Petersson and Karl-Eric Magnusson at Linköping U. in Linköping, Sweden; Thomas Norberg at Swedish U. of Agricultural Sciences, in Uppsala, Sweden; Frank Lindh at IsoSep AB, in Tullinge, Sweden; and Lennart Hammarström at the Karolinska Institute, in Huddinge, Sweden.
This research was supported by Umeå University Biotechnology Fund, Swedish Society of Medicine/Bengt Ihre's Fund, Swedish Society for Medical Research, Lion's Cancer Research Foundation at Umeå U., County Council of Västerbotten, the Neose Glycoscience Research Award Grant, Swedish Medical Research Council, Swedish Research Council, Swedish Cancer Society, SSF programs, J.C. Kempe Memorial Foundation, Wallenberg Foundation, Lundberg Foundation, Alf Grant Lund University Hospital, and the U.S. National Institutes of Health.
Journal
Science