Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Xiaoyun Liu
PROVIDER: PXD048666 | iProX | Thu Jan 18 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Toxoplasma gondii tachyzoites co-opt host cell functions through introduction of a large set of rhoptry- and dense granule-derived effector proteins. These effectors reach the host cytosol through different means: direct injection for rhoptry effectors and translocation across the parasitophorous vacuolar membrane (PVM) for dense granule (GRA) effectors. The machinery that translocates these GRA effectors has recently been partially elucidated, revealing 3 components, MYR1, MYR2 and MYR3. To determine if other proteins might be involved, we returned to a library of mutants defective in GRA translocation and selected one that has a partial defect, suggesting it might be in a gene encoding a new component of the machinery. Whole-genome sequencing showed that this mutant indeed has a missense mutation in a gene encoding a known serine/threonine protein kinase, ROP17, which has not previously been reported to be involved in GRA translocation. ROP17 resides at the PVM in infected cells and has previously been known for its activity in phosphorylating and, thereby, inactivating host immunity-related GTPases. Here, we show that null or catalytically dead mutants of ROP17 are defective in GRA translocation across the PVM, and that translocation across the PVM surrounding a Δrop17 mutant can be rescued “in trans” by ROP17 delivered by other tachyzoites infecting the same host cell. This strongly argues for a role for ROP17 at the PVM, not within the parasites or parasitophorous vacuole space. Hence, ROP17 plays a crucial part in GRA translocation, adding another function to the role it plays in modulating the interaction of Toxoplasma tachyzoites and the infected host cell.
2019-07-02 | GSE133144 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE26473: Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila [exp1] GSE26490: Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila [exp2] Refer to individual Series
2011-01-08 | E-GEOD-26491 | biostudies-arrayexpress
Project description:Many human Gram-negative bacterial pathogens express a Type Three Secretion Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC). These bacteria express on their surface multiple copies of the T3SA that mediate the delivery into host cells of specific protein substrates critical to pathogenesis. Shigella spp. are Gram-negative bacterial pathogens responsible for human bacillary dysentery. The effector function of several Shigella T3SA substrates has largely been studied but their potential cellular targets are far from having been comprehensively delineated. In addition, it is likely that some T3SA substrates have escaped scrutiny as yet. Indeed, sequencing of the virulence plasmid of Shigella flexneri has revealed numerous open reading frames with unknown functions that could encode additional T3SA substrates. Taking advantage of label-free mass spectrometry detection of proteins secreted by a constitutively secreting strain of S. flexneri, we identified five novel substrates of the T3SA. We further confirmed their secretion through the T3SA and translocation into host cells using b-lactamase assays. The coding sequences of two of these novel T3SA substrates (Orf13 and Orf131a) have a guanine-cytosine content comparable to those of T3SA components and effectors. The three other T3SA substrates identified (Orf48, Orf86 and Orf176) have significant homology with antitoxin moieties of type II Toxin-Antitoxin systems usually implicated in the maintenance of low copy plasmids. While Orf13 and Orf131a might constitute new virulence effectors contributing to S. flexneri pathogenicity, potential roles for the translocation into host cells of antitoxins or antitoxin-like proteins during Shigella infection are discussed.
2017-10-17 | PXD006086 | Pride
Project description:The intracellular bacterial pathogen Legionella pneumophila causes an inflammatory pneumonia called Legionnaires’ Disease. For virulence, L. pneumophila requires a Dot/Icm type IV secretion system that translocates bacterial effectors to the host cytosol. L. pneumophila lacking the Dot/Icm system is recognized by Toll-like receptors (TLRs), leading to a canonical NF-κB-dependent transcriptional response. In addition, L. pneumophila expressing a functional Dot/Icm system potently induces unique transcriptional targets, including proinflammatory genes such as Il23a and Csf2. Here we demonstrate that this Dot/Icm-dependent response, which we term the effector-triggered response (ETR), requires five translocated bacterial effectors that inhibit host protein synthesis. Upon infection of macrophages with virulent L. pneumophila, these five effectors caused a global decrease in host translation, thereby preventing synthesis of IκB, an inhibitor of the NF-κB transcription factor. Thus, macrophages infected with wildtype L. pneumophila exhibited prolonged activation of NF-κB, which was associated with transcription of ETR target genes such as Il23a and Csf2. L. pneumophila mutants lacking the five effectors still activated TLRs and NF-κB, but because the mutants permitted normal IκB synthesis, NF-κB activation was more transient and was not sufficient to fully induce the ETR. L. pneumophila mutants expressing enzymatically inactive effectors were also unable to fully induce the ETR, whereas multiple compounds or bacterial toxins that inhibit host protein synthesis via distinct mechanisms recapitulated the ETR when administered with TLR ligands. Previous studies have demonstrated that the host response to bacterial infection is induced primarily by specific microbial molecules that activate TLRs or cytosolic pattern recognition receptors. Our results add to this model by providing a striking illustration of how the host immune response to a virulent pathogen can also be shaped by pathogen-encoded activities, such as inhibition of host protein synthesis. Three-condition experiment: macrophages left uninfected (negative control), or infected with wildtype Legionella pneumophila, or the mutant Δ5, which lacks five bacterial effectors involved in inhibition of host protein synthesis (lgt1, lgt2, lgt3, sidI, sidL) (two experimental conditions). Biological replicates: two, independently infected, harvested, and hybridized to arrays. One technical replicate per array.
2011-01-08 | E-GEOD-26490 | biostudies-arrayexpress
Project description:The intracellular bacterial pathogen Legionella pneumophila (L.p.) manipulates eukaryotic host ubiquitination machinery to form its replicative vacuole. While nearly 10% of L.p.’s ∼330 secreted effector proteins are ubiquitin ligases or deubiquitinases, a comprehensive measure of temporally resolved changes in the endogenous host ubiquitinome during infection has not been undertaken. To elucidate how L.p hijacks host cell ubiquitin signaling, we generated a proteome-wide analysis of changes in protein ubiquitination during infection. We discover that L.p. infection increases ubiquitination of host regulators of subcellular trafficking and membrane dynamics, most notably ∼40% of mammalian Ras superfamily small GTPases. We determine that these small GTPases undergo non-degradative ubiquitination at the Legionella-containing vacuole membrane. Finally, we find that the bacterial effectors SidC/SdcA play a central role in cross-family small GTPase ubiquitination, and that these effectors function upstream of SidE-family ligases in the poly-ubiquitination and retention of GTPases in the LCV membrane. This work highlights the extensive reconfiguration of host ubiquitin signaling by bacterial effectors during infection and establishes simultaneous ubiquitination of small GTPases across the Ras superfamily as a novel consequence of L.p. infection. Our findings position L.p. as a tool to better understand how small GTPases can be regulated by ubiquitination in uninfected contexts.
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Project description:We measured expression level changes associated with the introduction of the F plasmid in 2 bacterial host strains (MG1655 and DH5alpha)
2008-06-11 | E-GEOD-1154 | biostudies-arrayexpress
Project description:The intracellular bacterial pathogen Legionella pneumophila causes an inflammatory pneumonia called Legionnaires’ Disease. For virulence, L. pneumophila requires a Dot/Icm type IV secretion system that translocates bacterial effectors to the host cytosol. L. pneumophila lacking the Dot/Icm system is recognized by Toll-like receptors (TLRs), leading to a canonical NF-κB-dependent transcriptional response. In addition, L. pneumophila expressing a functional Dot/Icm system potently induces unique transcriptional targets, including proinflammatory genes such as Il23a and Csf2. Here we demonstrate that this Dot/Icm-dependent response, which we term the effector-triggered response (ETR), requires five translocated bacterial effectors that inhibit host protein synthesis. Upon infection of macrophages with virulent L. pneumophila, these five effectors caused a global decrease in host translation, thereby preventing synthesis of IκB, an inhibitor of the NF-κB transcription factor. Thus, macrophages infected with wildtype L. pneumophila exhibited prolonged activation of NF-κB, which was associated with transcription of ETR target genes such as Il23a and Csf2. L. pneumophila mutants lacking the five effectors still activated TLRs and NF-κB, but because the mutants permitted normal IκB synthesis, NF-κB activation was more transient and was not sufficient to fully induce the ETR. L. pneumophila mutants expressing enzymatically inactive effectors were also unable to fully induce the ETR, whereas multiple compounds or bacterial toxins that inhibit host protein synthesis via distinct mechanisms recapitulated the ETR when administered with TLR ligands. Previous studies have demonstrated that the host response to bacterial infection is induced primarily by specific microbial molecules that activate TLRs or cytosolic pattern recognition receptors. Our results add to this model by providing a striking illustration of how the host immune response to a virulent pathogen can also be shaped by pathogen-encoded activities, such as inhibition of host protein synthesis. Four-condition experiment: macrophages left uninfected (negative control), or infected with wildtype Legionella pneumophila, the flagellin-deficient mutant ΔflaA, or the secretion-deficient mutant ΔdotA (three experimental conditions). Biological replicates: two, independently infected, harvested, and hybridized to arrays. One to two technical replicates per array, as indicated in file titles.
2011-01-08 | E-GEOD-26473 | biostudies-arrayexpress
Project description:We measured expression level changes associated with the introduction of the F plasmid in 2 bacterial host strains (MG1655 and DH5alpha) Keywords: parallel sample
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Project description:Due to low numbers and poor accessibility of host cells that are targeted for effector delivery, the actual biological functions of most effectors remain elusive. Here, we developed a novel Isolation Nuclei TArgeted by Bacterial Effectors (INTABE) system, which facilitates selectively recovering nuclei of the cells in Arabidopsis thaliana plants that have received type-III effectors of pathogenic Xanthomonas bacteria. Using these nuclei as studying materials, we analysed changes in host gene expression and their correlation with changes in DNA methylation induced by Xanthomonas effector Outer Protein D (XopD).
2022-10-22 | E-MTAB-10281 | biostudies-arrayexpress
Project description:Due to low numbers and poor accessibility of host cells that are targeted for effector delivery, the actual biological functions of most effectors remain elusive. Here, we developed a novel Isolation Nuclei TArgeted by Bacterial Effectors (INTABE) system, which facilitates selectively recovering nuclei of the cells in Arabidopsis thaliana plants that have received type-III effectors of pathogenic Xanthomonas bacteria. Using these nuclei as studying materials, we analysed changes in host gene expression and their correlation with changes in DNA methylation induced by Xanthomonas effector Outer Protein D (XopD).
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