The Dynamic Interactions between Salmonella and the Microbiota, within the Challenging Niche of the Gastrointestinal Tract

Figure 3

Salmonella use a variety of elegant strategies to compete with the intestinal microbiota. During the early stages of intestinal infection, Salmonella are able to scavenge the hydrogen produced by the microbiota to fuel initial growth. Microbiota produced short chain fatty acids (SCFAs) can modulate the expression of Salmonella SPI-1 invasion genes both positively (formate) and negatively (butyrate). Using the SPI-1 and SPI-2 type 3 secretion systems, S. Typhimurium are not only able to promote invasion and survival within host cells but also able to strategically elicit a host inflammatory response, which ultimately benefits the pathogen. The microbiota produces hydrogen sulfide, which normally becomes detoxified by host cells to thiosulfate. An inflammatory response leads to the transmigration of neutrophils into the intestinal lumen and the subsequent release of reactive oxygen species (ROS). When thiosulfate is exposed to ROS it is oxidized to tetrathionate, which can be exclusively used by S. Typhimurium as an alternative electron acceptor. S. Typhimurium can now utilize alternative carbon sources from the host, such as ethanolamine, using tetrathionate in anaerobic respiration. The inflammatory response results in the release of cytokines such as interferon-gamma (IFNγ). This results in the induction of expression of inducible nitric oxide synthase (iNOS), which generates nitric oxide. Upon exposure to superoxide free radicals nitric oxide is generated, and when exposed to ROS nitric oxide is converted to peroxynitrite and then nitrate. Nitrate can be used exclusively by S. Typhimurium, as an alternative electron acceptor during anaerobic respiration. This leads to an enormous growth burst in the pathogen leading to dysbiosis. Nitrate is thermodynamically the preferred electron acceptor over tetrathionate.