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Salmonella outwits immune system

UC DAVIS (US) — The bacteria Salmonella enterica—a common cause of food poisoning—exploits the immune response in the human gut to enhance its own survival.

The strategy, which improves reproductive and transmission success, gives Salmonella a growth advantage over the beneficial bacteria that normally are present in the intestinal tract, researchers report in the journal Nature. This advantage promotes the severe diarrhea that spreads the bacteria to other people.

“The human body normally has 10 times more microbes than human cells that help protect us against infection from disease-causing bacteria,” says Andreas Bäumler, professor of medical microbiology and immunology at the University of California, Davis, and the study’s principal investigator.

“We have discovered Salmonella’s cunning trick that allows it to quickly take over and outgrow the beneficial microbes in our intestine.”

All bacteria must generate energy in order to live and reproduce, either by respiration—which usually requires oxygen—or fermentation.

Because essentially no oxygen is available in our intestines, the beneficial bacteria that reside there tend to use fermentation, which is less efficient than respiration for obtaining energy.

When people ingest Salmonella, it invades the surface of the intestine. Our immune system responds by producing oxygen radicals to kill the bacteria.

Although some Salmonella bacteria are killed by this response, many more benefit: the oxygen radicals create a sulfur compound called tetrathionate, which Salmonella are able to use instead of oxygen for respiration.

Interestingly, tetrathionate has been used since 1923 by microbiologists as a way to promote the growth of Salmonella in biological samples containing competing microbes.

But because tetrathionate was not known to exist in living people, it was assumed prior to this study that this process had little relevance for food poisoning.

Up until now, tetrathionate was believed to mainly exist naturally in decaying corpses or in thermal springs.

“Stimulating the host to produce tetrathionate enables Salmonella to ‘breathe’ in the intestine,” says Sebastian Winter, who is a member of Bäumler’s laboratory and lead author of the article.

“This gives Salmonella a tremendous advantage over the gut bacteria that must grow by fermentation.”

By stimulating an inflammatory response in the intestine, Salmonella also enhances its transmission to other hosts. The inflammatory response causes the severe diarrhea and vomiting that is the body’s attempt to rid itself of the pathogenic bacteria, at the same time enabling Salmonella’s spread.

“Determining how Salmonella is so efficient in outcompeting resident beneficial bacteria is a critical first step in developing new drugs for treating food poisoning,” says Bäumler, whose group is now pursuing this avenue of research.

“We are hopeful that by targeting sulfur compounds we can stop the bacteria from establishing a foothold in the intestine.”

Additional researchers at UC Davis and Texas A&M University contributed to the work, which was funded by Public Health Service grants.

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