Salmonella enterica serovars Typhimurium and Typhi as model organisms: revealing paradigm of host-pathogen interactions

Abstract

The lifestyle of intracellular pathogens has always questioned the skill of a microbiologist in the context of finding the permanent cure to the diseases caused by them. The best tool utilized by these pathogens is their ability to reside inside the host cell, which enables them to easily bypass the humoral immunity of the host, such as the complement system. They further escape from the intracellular immunity, such as lysosome and inflammasome, mostly by forming a protective vacuole-bound niche derived from the host itself. Some of the most dreadful diseases are caused by these vacuolar pathogens, for example, tuberculosis by Mycobacterium or typhoid fever by Salmonella. To deal with such successful pathogens therapeutically, the knowledge of a host-pathogen interaction system becomes primarily essential, which further depends on the use of a model system. A well characterized pathogen, namely Salmonella, suits the role of a model for this purpose, which can infect a wide array of hosts causing a variety of diseases. This review focuses on various such aspects of research on Salmonella which are useful for studying the pathogenesis of other intracellular pathogens.

Figure 2. Breaching of gut epithelia by Salmonella. The mode of entry of Salmonella in gut lumen varies according to type of cell encountered on the gut epithelium. The M cells take up the bacteria by means of receptor mediated endocytosis, whereas dendritic cells engulf them by phagocytosis. The membrane of epithelial cells is modified by the action of SPI1 to facilitate the entry of bacteria. Once inside the gut lumen, Salmonella is being taken up by macrophages, T cells, B cells, neutrophils, etc.

Figure 1. Challenges encountered by Salmonella. The text boxes represent the various stresses encountered by Salmonella during its life cycle and the open text describes the factors and signals generated by Salmonella in order to combat these stress conditions.

Figure 3. Immune evasion strategies of Salmonella. The intracellular life-cycle of Salmonella includes the entry of the bacterium in the host cell, SCV formation (whose pH changes from 6.5 to 5.5 depicted by change in the color of SCV compartment), evasion of host immune response and ultimately host cell death by apoptosis. The text in dark blue shows the immune responses and processes within the host cell that take place during Salmonella infection and text in dark red depicts the factors that help Salmonella to evade these immune responses.