The role of the type III secretion system in the intracellular lifestyle of enteric pathogens

Several pathogens have evolved to infect host cells from within, which requires subversion of many host intracellular processes. In the case of Gram-negative pathogenic bacteria, adaptation to an intracellular life cycle relies largely on the activity of type III secretion systems (T3SSs), an apparatus used to deliver effector proteins into the host cell, from where these effectors regulate important cellular functions such as vesicular trafficking, cytoskeleton reorganization, and the innate immune response. Each bacterium is equipped with a unique suite of these T3SS effectors, which aid in the development of an individual intracellular lifestyle for their respective pathogens. Some bacteria adapt to reside and propagate within a customized vacuole, while others establish a replicative niche in the host cytosol. In this article, we review the mechanisms by which T3SS effectors contribute to these different lifestyles. To illustrate the formation of a vacuolar and a cytosolic lifestyle, we discuss the intracellular habitats of the enteric pathogens Salmonella enterica serovar Typhimurium and Shigella flexneri, respectively. These represent wellcharacterized systems that function as informative models to contribute to our understanding of T3SS-dependent subversion of intracellular processes. Additionally, we present Vibrio parahaemolyticus, another enteric Gramnegative pathogen, as an emerging model for future studies of the cytosolic lifestyle.