New research from scientists at UC Davis Health provides clues for how friendly bacteria in the gut–probiotics–may help eradicate bacterial pathogens like Salmonella by competing with them for needed resources.
The study, published today in Cell Host & Microbe, shows that the availability of needed nutrients alone doesn’t define where bacteria–including pathogens like Salmonella–can survive and thrive in the gut.
” These insights provide a better understanding about the nutritional basis for intestinal colonization and can inform efforts to develop antibiotics to combat infection,” Megan Liou (a Ph.D. candidate at UC Davis) and the first author.
Humans can only use oxygen, the air we breathe, to generate energy. However, microbes have developed energy mechanisms that allow them to “breathe” other compounds and elements such as nitrates. These mechanisms allow microbes to survive in many different environments.
In the study, the researchers looked at a friendly strain of bacteria, Escherichia coli strain Nissle 1917 (E. coli), and Salmonella, a harmful strain of bacteria that can cause gastrointestinal illness in humans and animals. (Some strains of E. Coli can cause illness, but most are harmless. )
Microbes use nitrate for energy
Nitrate, which is best known for its role as a food additive, is also an important resource to microbes in the gut. The nitrate from food sources is absorbed in the small intestine. As a byproduct of daily metabolic processes, nitrate can also be found in the small intestine. Although it is usually very low, it increases with inflammation.
Both strains of bacteria in the gut use nitrate as energy. But the researchers found that Salmonella can only use nitrate generated by phagocytes, a specific type of immune cells the body sends to repair wounded or infected tissues.
The E. coli uses nitrate generated by both gut cells–epithelial tissue–and phagocytes, meaning that it can compete with the Salmonella for its energy source.
Liou has compared these sources of nitrates with different “restaurants” in which microbes can get the resources they need for growth.
“The ability of E. coli Nissle to dine at ‘restaurants’ generated by phagocytes and compete with the pathogen for resources was essential for the probiotic to confer protection against Salmonella,” Liou said.
When the researchers infected mice with Salmonella, it triggered the expected inflammation in the gut, resulting in immune cells–phagocytes–being brought into the intestinal lumen, the layer that lines the intestines. Salmonella was able to find a niche in the lining of the intestines rich in phagocytes and exclusively used the nitrates generated by these immune cells.
Sensors limit where Salmonella can get resources in the gut
One puzzling aspect of the competition between the probiotic E. coli and the disease-inducing Salmonella was why the Salmonella did not utilize the nitrate produced by the healthy gut tissue. It used only the nitrate from the immune-response tissues, restricting the places it could “dine”.
The researchers found the answer in the sensors of Salmonella that allow the bacteria to sniff out its surroundings and move toward a more favorable environment, known as chemotaxis receptors. They directed the pathogen away of the epithelial-derived Nitrate and towards the inflammatory phagocytes.
Essentially, the Salmonella did not have a sensing mechanism that would steer it toward the healthy epithelial tissue, even though that tissue also created nitrates. The probiotic E. coli lacks chemotaxis receptors, which allows it to occupy both niches and compete against the pathogen in the latter’s favored environm