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Review
. 2011 Nov;68(22):3687-97.
doi: 10.1007/s00018-011-0841-0. Epub 2011 Oct 9.

Salmonella effector proteins and host-cell responses

C V Srikanth  1 , Regino Mercado-Lubo, Kelly Hallstrom, Beth A McCormick
Affiliations
Review

Salmonella effector proteins and host-cell responses

C V Srikanth et al. Cell Mol Life Sci. 2011 Nov.

Abstract

Acute gastroenteritis caused by Salmonella enterica serovar typhimurium is a significant public health problem. This pathogen has very sophisticated molecular machinery encoded by the two pathogenicity islands, namely Salmonella Pathogenicity Island 1 and 2 (SPI-1 and SPI-2). Remarkably, both SPI-1 and SPI-2 are very tightly regulated in terms of timing of expression and spatial localization of the encoded effectors during the infection process within the host cell. This regulation is governed at several levels, including transcription and translation, and by post-translational modifications. In the context of a finely tuned regulatory system, we will highlight how these effector proteins co-opt host signaling pathways that control the ability of the organism to infect and survive within the host, as well as elicit host pro-inflammatory responses.

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Figures

Fig. 1
Fig. 1
Spatial dynamics of Salmonella effectors during infection. Secretion of effectors and their action begin prior to bacteria entry. SipA secretion leads to activation of caspase-3, which may act as the starting point of the inflammatory pathways induced by the bacteria. Upon contact with epithelial cells, the bacteria translocate early effectors through the type three secretion system encoded by Salmonella pathogenicity island-1 (SPI-1, green circles). This leads to the induction of pathways that activate the transcription factors AP-1 and NF-κB. These processes trigger major cytoskeletal rearrangements, resulting in bacterial entry into the epithelial cells along with the basolateral release of interleukin 8 (IL-8), which is a crucial step in polymorpho mononeuclear leukocyte (PMNs) recruitment. SipA and other proinflammatory effectors induce the PKCα driven pathway of eiconasoid biosynthesis, which culminates in the apical release of hepoxilin-A3 (HXA3). HXA3 forms a gradient along the paracellular space, which guides PMNs to the apical surface of the epithelium, a process that also damages the epithelial layer. Endocytosed bacteria remain in a spacious vacuole called the Salmonella-containing vacuole (SCV). At this point, several effectors, such as SptP and SspH1, function to re-establish homeostasis by inhibiting proinflammatory mechanisms. Bacteria within the SCV secrete effectors through another type III secretion system encoded by Salmonella pathogenicity island-2 (SPI-2, blue circles). These effectors promote the stability of the SCV and the survival of bacteria within the SCV. Also seen in the schematic is the persistence of some SPI-1 effectors even after the formation of SCV
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