Functions of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system effectors

Figueira, R.C.S.; Holden, David W.

doi:10.1099/mic.0.058115-0

Cited by 295 publications

(278 citation statements)

References 152 publications

(158 reference statements)

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“…2, B and C; Table I). These results agree with previous findings where the main functions of SPI2 T3SS are thought to promote intracellular replication inside macrophages by altering host vesicular trafficking, cytoskeleton, and immune signaling (3,4). Furthermore, these findings suggest that these cellular processes/pathways in RAW264.7 cells are principally regulated by SPI2 effectors at the phosphoproteome level.…”

Section: Quantitative Phosphoproteome and Proteome Profiling Of The Hsupporting

confidence: 83%

“…Specifically, macrophages appear to be more broadly impacted than epithelial cells, consistent with a role for SPI2 T3SS as a main modulator for phagocytic cells (3)(4)(5).…”

Section: Quantitative Phosphoproteome and Proteome Profiling Of The Hmentioning

confidence: 63%

“…Approximately 30 effectors are known to be translocated by the SPI2 T3SS but the actions and targets of most of these effectors are largely unknown (1,3,4). A recent systematic study using a single mutant collection of SPI2 genes showed particular virulence factors (e.g.…”

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confidence: 99%

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Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome

Imami

Bhavsar

et al. 2013

Molecular & Cellular Proteomics

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During the late stages of infection, Salmonella secretes numerous effectors through a type III secretion system that is encoded within Salmonella pathogenicity island 2 (SPI2). Despite the importance of SPI2 as a major virulence factor leading to the systemic spread of the bacteria and diseases, a global view of its effects on host responses is still lacking. Here, we measured global impacts of SPI2 effectors on the host phosphorylation and protein expression levels in RAW264.7 and in HeLa cells, as macrophage and nonphagocytic models of infection. We observe that SPI2 effectors differentially modulate the host phosphoproteome and cellular processes (e.g. protein trafficking, cytoskeletal regulation, and immune signaling) in a host cell-dependent manner. Our unbiased approach reveals the involvement of many previously unrecognized proteins, including E3 ligases (HERC4, RanBP2, and RAD18), kinases (CDK, SIK3, and WNK1), and histones (H2B1F, H4, and H15), in late stages of Salmonella infection. Furthermore, from this phosphoproteome analysis and other quantitative screens, we identified HSP27 as a direct in vitro and in vivo molecular target of the only type III secreted kinase, SteC. Using biochemical and cell biological assays, we demonstrate that SteC phosphorylates multiple sites in HSP27 and induces actin rearrangement through this protein. Together, these results provide a broader landscape of host players contributing to specific processes/pathways mediated by SPI2 effectors than was previously appreciated. Molecular &

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Section: Quantitative Phosphoproteome and Proteome Profiling Of The Hsupporting

confidence: 83%

“…Specifically, macrophages appear to be more broadly impacted than epithelial cells, consistent with a role for SPI2 T3SS as a main modulator for phagocytic cells (3)(4)(5).…”

Section: Quantitative Phosphoproteome and Proteome Profiling Of The Hmentioning

confidence: 63%

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Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome

Imami

Bhavsar

et al. 2013

Molecular & Cellular Proteomics

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“…Salmonella enteritica serovar Typhimurium (S. Typhimurium) causes self-limiting gastroenteritis in humans and systemic disease in susceptible mice. As a facultative intracellular bacterium, Salmonella uses virulence factors encoded in the Salmonella pathogenicity islands SPI-1 and SPI-2 to invade and replicate inside host cells, including macrophages and epithelial cells (reviewed in Figueira and Holden, 2012). Injection of mouse ASC-derived intestinal organoids, as well as human iPSC-derived intestinal organoids, with S. Typhimurium resulted in the upregulation of host cell genes, including typical proinflammatory cytokines such as IL-1β, TNF and IL-8 (Forbester et al, 2015;Zhang et al, 2014).…”

Section: Anaerobic Bacteriamentioning

confidence: 99%

Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids

Bartfeld

2016

Developmental Biology

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“…These activities are heavily mediated by the use of type-three secretion systems (T3SS), which function as molecular syringes to penetrate host cells and deliver bacterial effector proteins into the host cytoplasm ( Figure 2). These effector proteins typically recognise specific host proteins, and disrupt the normal function of these proteins often by catalysing post-translational modifications 19,20 .…”

Section: Salmonella Subverts Host Cells To Achieve Infectionmentioning

confidence: 99%

Salmonella in Australia: understanding and controlling infection

Newson¹

2017

Microbiol. Aust.

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The bacterium Salmonella causes a spectrum of foodborne diseases ranging from acute gastroenteritis to systemic infections, and represents a significant burden of disease globally. In Australia, Salmonella is frequently associated with outbreaks and is a leading cause of foodborne illness, which results in a significant medical and economic burden. Salmonella infection involves colonisation of the small intestine, where the bacteria invades host cells and establishes an intracellular infection. To survive within host cells, Salmonella employs type-three secretion systems to deliver bacterial effector proteins into the cytoplasm of host cells. These bacterial effectors seek out and modify specific host proteins, disrupting host processes such as cell signalling, intracellular trafficking, and programmed cell death. This strategy of impairing host cells allows Salmonella to establish a replicative niche within the cell, where they can replicate to high numbers before escaping to infect neighbouring cells, or be transmitted to new hosts. While the importance of effector protein translocation to infection is well established, our understanding of many effector proteins remains incomplete. Many Salmonella effectors have unknown function and unknown roles during infection. A greater understanding of how Salmonella manipulates host cells during infection will lead to improved strategies to prevent, control, and eliminate disease. Further, studying effector proteins can be a useful means for exploring host cell biology and elucidating the details of host cell signalling.

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Functions of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system effectors

Cited by 295 publications

References 152 publications

Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome

Global Impact of Salmonella Pathogenicity Island 2-secreted Effectors on the Host Phosphoproteome

Modeling infectious diseases and host-microbe interactions in gastrointestinal organoids

Salmonella in Australia: understanding and controlling infection

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