Salmonella exploits immune system to establish itself in the gut

Salmonella exploits immune system to establish itself in the gut

New research led by the University of California (UC) Davis suggests that Salmonella bacteria exploit a defence mechanism in the human immune system to set up camp in our intestines: the inflammation response they trigger when they enter the gut gives them a chemical that helps them outgrow beneficial microbes and promote the severe diarrhea that helps them spread to other hosts.

You can read how principal investigator Dr Andreas Bäumler, professor of medical microbiology and immunology at the UC Davis School of Medicine, and colleagues, discovered how Salmonella does this in a paper published on 23 September in the journal Nature.

Bäumler said in a statement that:

"The human body normally has 10 times more microbes than human cells that help protect us against infection from disease-causing bacteria."

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

There are two ways bacteria get energy to survive, grow and replicate: respiration, which normally uses oxygen, or fermentation, which is less efficient.

Our gut does not have a ready supply of oxygen that gut bacteria can use, and the ones that live there have adapted to getting their energy by fermentation.

In their study, Bäumler and colleagues found that Salmonella Typhimurium causes acute gut inflammation by invading the surface of the gut wall where it survives in "mucosal macrophages".

This invasion prompts the immune system to produce oxygen radicals to kill the bacteria. This is partially successful in that some Salmonella bacteria do indeed perish, but many more actually benefit from this mechanism, because the oxygen radicals produce a sulphur compound called tetrathionate, which the remaining Salmonella use instead of oxygen for respiration.

The authors wrote that:

"The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut."

What is interesting about this discovery is that we've known since 1923 that tetrathionate helps Salmonella outgrow competing microbes in lab cultures.

What we didn't know was that the compound also exists in the guts of living people, and thus might play a role in food poisoning. (Until now, scientists thought it existed mainly in decaying corpses and thermal springs).

Bäumler and colleagues concluded that:

"... S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes."

They suggested that Salmonella's ability to trigger inflammation in the gut is "crucial for the biology of this diarrhoeal pathogen".

Lead author Dr Sebastian E. Winter, a member of Bäumler's lab team, said that being able to use tetrathionate gives Salmonella's a considerable survival advantage over the microbes that survive by fermentation.

By creating an inflammatory response, the bacteria also ensures it gets passed onto other hosts, because the inflammation causes severe diarrhea and vomiting.

For the study, the researchers used test tube cultures and laboratory mice bred to enable them to study conditions similar to the human gut. They used methods from a new and expanding field, metabolomics: the study of metabolites in living organisms.

Infection by Salmonella causes an illness known as salmonellosis, one of the most common forms of food poisoning. The symptoms include diarrhea, fever, vomiting and abdominal cramps. Although most people don't experience a severe illness and recover in a few days, vulnerable groups such as the very young, the very old and people with weakened immune systems can get very ill and deaths can occur.

The findings of this study have important implications for the treatment of salmonellosis: in most cases you can't use antibiotics because they also kill the beneficial microbes and that just prolongs the illness.

The way that Salmonella exploits tetrathionate could provide a target for new treatments that don't kill off the beneficial bacteria.

Bäumler also said that:

"Determining how Salmonella is so efficient in outcompeting resident beneficial bacteria is a critical first step in developing new drugs for treating food poisoning."

"We are hopeful that by targeting sulfur compounds we can stop the bacteria from establishing a foothold in the intestine," he added.

He and his team have already started investigating this.

"Gut inflammation provides a respiratory electron acceptor for Salmonella."

Sebastian E. Winter, Parameth Thiennimitr, Maria G. Winter, Brian P. Butler, Douglas L. Huseby, Robert W. Crawford, Joseph M. Russell, Charles L. Bevins, L. Garry Adams, Renée M. Tsolis, et al.

Nature, Volume 467, Pages 426-429, published online 23 September 2010.


Additional source: UC Davis.

Facets of Discovery: [email protected] (Video Medical And Professional 2020).

Section Issues On Medicine: Disease