Salmonella Modulation of Host Cell Gene Expression Promotes Its Intracellular Growth

Abstract

Salmonella Typhimurium has evolved a complex functional interface with its host cell largely determined by two type III secretion systems (T3SS), which through the delivery of bacterial effector proteins modulate a variety of cellular processes. We show here that Salmonella Typhimurium infection of epithelial cells results in a profound transcriptional reprogramming that changes over time. This response is triggered by Salmonella T3SS effector proteins, which stimulate unique signal transduction pathways leading to STAT3 activation. We found that the Salmonella-stimulated changes in host cell gene expression are required for the formation of its specialized vesicular compartment that is permissive for its intracellular replication. This study uncovers a cell-autonomous process required for Salmonella pathogenesis potentially opening up new avenues for the development of anti-infective strategies that target relevant host pathways.

Dual RNA-seq of pathogen and host

“…2.27) were found to be up-regulated also in previous studies (e.g. Bruno et al, 2009;Hannemann et al, 2013). Other early induced mRNAs such as IL6…”

“…Therefore, observations that STnc440 affects the level of Salmonella virulence effectors from SPI-1 (Y. Chao, personal communication) and SPI-2 (see above), implied that also the host response to infection could be influenced by the action of this sRNA (Bruno et al, 2009;Hannemann et al, 2013;Nikai, 2005, 2008). (Yoshimura et al, 2007).…”

“…In turn, microarrays yielded important insights into the global response of potential mammalian hosts upon cytokine (Zhu et al, 1998) or pathogen-associated molecular pattern (PAMP) stimulation (Hedges et al, 2005;Kerns et al, 2009;Tross et al, 2009), as well as towards diverse bacterial (reviewed in Rappuoli, 2000) or viral infections (Der et al, 1998). Recently, two microarray-based studies reported the response of human epithelial cells to S. Typhimurium infection and found that by secreting effector proteins Salmonella induces pervasive transcriptional reprogramming in the host (Bruno et al, 2009;Hannemann et al, 2013). Less frequently, tag-based approaches have been applied to the field of infection biology, e.g.…”

“…Likewise the host response to live bacterial challenge was found to be more complex than that towards individual PAMPs (e.g. Hannemann et al, 2013). However, separation and enrichment are laborintensive, error-prone as additional steps in the protocol are considered potential sources of bias, and usually are incompatible with low amounts of starting material.…”

Scientific Opinion on the evaluation of molecular typing methods for major food‐borne microbiological hazards and their use for attribution modelling, outbreak investigation and scanning surveillance: Part 1 (evaluation of methods and applications)

“…Salmonella has evolved a complex functional interface with host cells largely determined by two type III secretion systems (T3SS). These are encoded within SPI1, which through the delivery of bacterial effector proteins modulates a variety of cellular processes that facilitate uptake into, and replication within, epithelial and phagocytic cells (Hannemann et al, 2013). Further virulence traits, such as the pSLT virulence plasmid, adhesins, flagellae, ion transporters, superoxide dismutase and biofilm-related proteins, also contribute to success within the host (Ibarra and Steele-Mortimer, 2009).…”