The Salmonella Effector SptP Dephosphorylates Host AAA+ ATPase VCP to Promote Development of its Intracellular Replicative Niche

Summary Virulence effectors delivered into intestinal epithelial cells by Salmonella trigger actin remodeling to direct pathogen internalization and intracellular replication in Salmonella-containing vacuoles (SCVs). One such effector, SptP, functions early during pathogen entry to deactivate Rho GTPases and reverse pathogen-induced cytoskeletal changes following uptake. SptP also harbors a C-terminal protein tyrosine phosphatase (PTPase) domain with no clear host substrates. Investigating SptP's longevity in infected cells, we uncover a late function of SptP, showing that it associates with SCVs, and its PTPase activity increases pathogen replication. Direct SptP binding and specific dephosphorylation of the AAA+ ATPase valosin-containing protein (VCP/p97), a facilitator of cellular membrane fusion and protein degradation, enhanced pathogen replication in SCVs. VCP and its adaptors p47 and Ufd1 were necessary for generating Salmonella-induced filaments on SCVs, a membrane fusion event characteristic of the pathogen replicative phase. Thus, Salmonella regulates the biogenesis of an intracellular niche through SptP-mediated dephosphorylation of VCP.

• Publication year

  2009

• Venue

  Cell Host and Microbe

• Publication date

  2009-03-19

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.chom.2009.01.010PMID 19286132PMCID 2724103
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Tyrosine phosphorylation of ATPase p97 regulates its activity during ERAD.

  2008cited by this paper
• Insights into adaptor binding to the AAA protein p97.

  2008cited by this paper
• Ubxd1 is a novel co-factor of the human p97 ATPase.

  2008cited by this paper
• The Salmonella-containing vacuole: moving with the times.

  2008cited by this paper
• UBX domain proteins: major regulators of the AAA ATPase Cdc48/p97

  2008cited by this paper
• Studies on peptide:N-glycanase–p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation

  2007cited by this paper
• Protein tyrosine phosphatase function: the substrate perspective.

  2007cited by this paper
• Structural insights into the p97-Ufd1-Npl4 complex

  2007cited by this paper
• Salmonella SPI1 Effector SipA Persists after Entry and Cooperates with a SPI2 Effector to Regulate Phagosome Maturation and Intracellular Replication

  2007influential reference
• Intracellular Salmonella enterica Redirect Exocytic Transport Processes in a Salmonella Pathogenicity Island 2‐Dependent Manner

  2006cited by this paper
• Diverse functions with a common regulator: ubiquitin takes command of an AAA ATPase.

  2006influential reference
• Differential activation and function of Rho GTPases during Salmonella–host cell interactions

  2006cited by this paper
• RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics

  2006cited by this paper
• p97 and close encounters of every kind: a brief review.

  2004cited by this paper
• Interactions underlying assembly of the Escherichia coli AcrAB–TolC multidrug efflux system

  2004cited by this paper
• Recognition of bacteria in the cytosol of Mammalian cells by the ubiquitin system.

  2004cited by this paper
• RNA interference of valosin-containing protein (VCP/p97) reveals multiple cellular roles linked to ubiquitin/proteasome-dependent proteolysis

  2004cited by this paper
• Salmonella Modulates Vesicular Traffic by Altering Phosphoinositide Metabolism

  2004cited by this paper
• The target cell plasma membrane is a critical interface for Salmonella cell entry effector–host interplay

  2004influential reference
• Control of actin turnover by a salmonella invasion protein.

  2004cited by this paper
• Bacterial Invasion: The Paradigms of Enteroinvasive Pathogens

  2004cited by this paper
• SseG, a virulence protein that targets Salmonella to the Golgi network

  2003cited by this paper
• Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation.

  2003cited by this paper
• Salmonella enterica serovar Typhimurium effector SigD/SopB is membrane‐associated and ubiquitinated inside host cells

  2002cited by this paper
• The invasion‐associated type III secretion system of Salmonella enterica serovar Typhimurium is necessary for intracellular proliferation and vacuole biogenesis in epithelial cells

  2002cited by this paper
• Disruption of the Salmonella-Containing Vacuole Leads to Increased Replication of Salmonella enterica Serovar Typhimurium in the Cytosol of Epithelial Cells

  2002cited by this paper
• Cooperation between actin‐binding proteins of invasive Salmonella: SipA potentiates SipC nucleation and bundling of actin

  2001cited by this paper
• Salmonella interactions with host cells: type III secretion at work.

  2001cited by this paper
• A role for the PhoP/Q regulon in inhibition of fusion between lysosomes and Salmonella‐containing vacuoles in macrophages

  2001cited by this paper
• Characterization of Salmonella‐Induced Filaments (Sifs) Reveals a Delayed Interaction Between Salmonella‐Containing Vacuoles and Late Endocytic Compartments

  2001cited by this paper
• Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells

  2001cited by this paper
• The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence

  2000cited by this paper
• Tyrosine phosphorylation of p97 regulates transitional endoplasmic reticulum assembly in vitro.

  2000cited by this paper
• Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.

  2000cited by this paper
• The rab7 GTPase controls the maturation of Salmonella typhimurium‐containing vacuoles in HeLa cells

  1999cited by this paper
• Biogenesis of Salmonella typhimurium‐containing vacuoles in epithelial cells involves interactions with the early endocytic pathway

  1999cited by this paper
• A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion

  1999cited by this paper
• Syntaxin 5 is a common component of the NSF- and p97-mediated reassembly pathways of Golgi cisternae from mitotic Golgi fragments in vitro.

  1998cited by this paper
• The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton

  1998cited by this paper
• Mechanism of Inhibition of Protein-tyrosine Phosphatases by Vanadate and Pervanadate*

  1997cited by this paper
• Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions

  1997cited by this paper
• Development of "substrate-trapping" mutants to identify physiological substrates of protein tyrosine phosphatases.

  1997cited by this paper
• A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurlum

  1996cited by this paper
• Biochemical characterization of valosin-containing protein, a protein tyrosine kinase substrate in hematopoietic cells.

  1994cited by this paper
• P97 and Close Encounters of Every Kind: a Brief Review

  year unknowncited by this paper

• Staphylococcus aureus utilizes vimentin to internalize human keratinocytes

  2025cites this paper
• Structural analysis of dual specificity phosphatases, the only type of protein tyrosine phosphatases found in humans and across diverse microorganisms.

  2025cites this paper
• Unravelling Salmonella Pathogenesis: Effector-Mediated Post-Translational Modifications, Alternative Therapies, and Advances in Rapid Detection.

  2025cites this paper
• Host AAA-ATPase VCP/p97 lyses ubiquitinated intracellular bacteria as an innate antimicrobial defence

  2025cites this paper
• Molecular Mimicry by Bacterial Effector Proteins

  2025cites this paper
• Infection biology of Salmonella enterica

  2024cites this paper
• The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP

  2023cites this paper
• The ever‐increasing necessity of mass spectrometry in dissecting protein post‐translational modifications catalyzed by bacterial effectors

  2023cites this paper
• Speaking the host language: how Salmonella effector proteins manipulate the host

  2023cites this paper
• p97/VCP targets Toxoplasma gondii vacuoles for parasite restriction in interferon-stimulated human cells

  2023cites this paper
• Inhibitors of the ATPase p97/VCP: From basic research to clinical applications.

  2023cites this paper
• Determination of the Salmonella intracellular lifestyle by the diversified interaction of Type III secretion system effectors and host GTPases.

  2022cites this paper
• Control of host PTMs by intracellular bacteria: An opportunity toward novel anti-infective agents.

  2022cites this paper
• Paratyphoid Fever A: Infection and Prevention

  2022cites this paper
• Salmonella-Based Biorodenticides: Past Applications and Current Contradictions

  2022cites this paper
• Characterization and protective efficacy of a sptP mutant of Salmonella Paratyphi A

  2020cites this paper
• Salmonella secretion systems: Differential roles in pathogen-host interactions.

  2020cites this paper
• Importance of protein Ser/Thr/Tyr phosphorylation for bacterial pathogenesis.

  2020cites this paper
• Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network

  2019cites this paper
• A trafficome-wide RNAi screen reveals deployment of early and late secretory host proteins and the entire late endo-/lysosomal vesicle fusion machinery by intracellular Salmonella

  2019cites this paper
• The Role of the Type III Secretion System in the Intracellular Lifestyle of Enteric Pathogens

  2019cites this paper
• Identification and characterization of a large family of superbinding bacterial SH2 domains

  2018cites this paper
• Typhoidal Salmonella: Distinctive virulence factors and pathogenesis

  2018cites this paper
• Identification and characterization of a large family of superbinding bacterial SH2 domains

  2018cites this paper
• Biochemische und strukturelle Einsichten der proteolytischen Modifikation kleiner GTPasen durch bakterielle Effektoren aus Salmonella enterica und Vibrio vulnificus

  2018cites this paper
• Interferon-γ in Salmonella pathogenesis: New tricks for an old dog.

  2017cites this paper
• The Type III Secretion System Effector SptP of <named-content content-type='genus-species'>Salmonella enterica</named-content> Serovar Typhi

  2017cites this paper
• Live Cell Methods to Visualize Translocated Salmonella Effectors and Monitor Ca2+ Transients During Infection

  2017cites this paper
• A novel method of transcriptome interpretation reveals a quantitative suppressive effect on tomato immune signaling by two domains in a single pathogen effector protein

  2016cites this paper
• The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi

  2016cites this paper
• Identification and characterization of interactions between bacterial WxxxE-virulence proteins and host cell proteins

  2016cites this paper
• Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter

  2016cites this paper
• Identification of Bostrycin Derivatives as Potential Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatase (MptpB).

  2016cites this paper
• Salmonellae interactions with host processes

  2015cites this paper
• Salmonella modulation of the phagosome membrane, role of SseJ

  2015cites this paper
• Protein Phosphatases of Pathogenic Bacteria: Role in Physiology and Virulence.

  2015cites this paper
• Salmonella Manipulates Autophagy to "Serve and Protect".

  2015cites this paper
• Salmonella and the oxidative burst : tales of a complicated relationship.

  2015cites this paper
• Structural insight into effector proteins of Gram‐negative bacterial pathogens that modulate the phosphoproteome of their host

  2015cites this paper
• Salmonella Typhimurium Impedes Innate Immunity With a Mast Cell-Suppressing Tyrosine Phosphatase Sptp

  2014cites this paper
• Salmonella Suppress Innate Immunity by Targeting Mast Cells

  2014cites this paper
• The Salmonella Typhimurium effector protein SopE transiently localizes to the early SCV and contributes to intracellular replication

  2014influential citation
• A Burkholderia cenocepacia gene encoding a non-functional tyrosine phosphatase is required for the delayed maturation of the bacteria-containing vacuoles in macrophages.

  2014cites this paper
• The SPI-1-like Type III secretion system: more roles than you think

  2014cites this paper
• Mechanisms of anaerobic nitric oxide detoxification by Salmonella enterica serovar Typhimurium

  2013cites this paper
• A Shigella effector dampens inflammation by regulating epithelial release of danger signal ATP through production of the lipid mediator PtdIns5P.

  2013cites this paper
• Structural basis of eukaryotic cell targeting by type III secretion system (T3SS) effectors.

  2013cites this paper
• Salmonella Pathogenicity Island 1(SPI-1) at Work

  2013cites this paper
• Small molecule tools for functional interrogation of protein tyrosine phosphatases

  2013cites this paper
• Regulation of small GTPases by GEFs, GAPs, and GDIs.

  2013cites this paper
• Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP.

  2013cites this paper
• Mycobacterium tuberculosis-secreted phosphatases: from pathogenesis to targets for TB drug development.

  2013cites this paper
• Bicyclic benzofuran and indole-based salicylic acids as protein tyrosine phosphatase inhibitors.

  2012cites this paper
• Impact of Salmonella enterica Type III Secretion System Effectors on the Eukaryotic Host Cell

  2012influential citation
• A luminescent reporter evidences active expression of Ralstonia solanacearum type III secretion system genes throughout plant infection.

  2012cites this paper
• THE VIRULENCE CHAPERONE NETWORK ASSOCIATED WITH THE SPI-2 ENCODED TYPE THREE SECRETION SYSTEM OF SALMONELLA ENTERICA

  2012cites this paper
• Type III effector-mediated processes in Salmonella infection.

  2012cites this paper
• Salmonella Virulence Effector SopE and Host GEF ARNO Cooperate to Recruit and Activate WAVE to Trigger Bacterial Invasion

  2012cites this paper
• Avirulence proteins AvrBs7 from Xanthomonas gardneri and AvrBs1.1 from Xanthomonas euvesicatoria contribute to a novel gene-for-gene interaction in pepper.

  2012cites this paper
• The current Salmonella‐host interactome

  2012cites this paper
• The Drosophila Arf1 homologue Arf79F is essential for lamellipodium formation

  2012cites this paper
• The late endosomal adaptor p14 is a macrophage host-defense factor against Salmonella infection

  2012cites this paper
• Proteomic analysis of Salmonella-host interactions reveals novel host targets of SopB

  2011cites this paper
• Subversion of membrane transport pathways by vacuolar pathogens

  2011cites this paper
• Functional domains and motifs of bacterial type III effector proteins and their roles in infection.

  2011cites this paper
• Salmonella – At Home in the Host Cell

  2011cites this paper
• Phosphoproteomic Analysis of Salmonella-Infected Cells Identifies Key Kinase Regulators and SopB-Dependent Host Phosphorylation Events

  2011cites this paper
• Citrus flavonoid represses Salmonella pathogenicity island 1 and motility in S. Typhimurium LT2.

  2011cites this paper
• Spotting the right location- imaging approaches to resolve the intracellular localization of invasive pathogens.

  2011cites this paper
• Salmonella Acquires Lysosome-associated Membrane Protein 1 (LAMP1) on Phagosomes from Golgi via SipC Protein-mediated Recruitment of Host Syntaxin6*

  2011cites this paper
• Cellular Functions of Ufd2 and Ufd3 in Proteasomal Protein Degradation Depend on Cdc48 Binding

  2011cites this paper
• Citrus bioactive compounds: Isolation, characterization and modulation of bacterial intercellular communication and virulence

  2011cites this paper
• Entwicklung einer Multi-Epitop-Vakzine auf Basis exponierter Peptiddomänen verschiedener Virulenz-assoziierter Außenmembranproteine uropathogener Escherichia coli

  2011cites this paper
• Identification et étude du rôle des protéines cibles du monoxyde d'azote (NO) dans les réponses de défense chez le tabac

  2011cites this paper
• Salmonella effectors: important players modulating host cell function during infection

  2011influential citation
• The phosphoinositide phosphatase SopB manipulates membrane surface charge and trafficking of the Salmonella-containing vacuole.

  2010influential citation
• New strategies in fighting TB: targeting Mycobacterium tuberculosis-secreted phosphatases MptpA & MptpB.

  2010cites this paper
• Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents

  2010cites this paper
• Salmonella characterization of the type III effector SrfH and proteomic identification of the secretome

  2010cites this paper
• Imaging Type-III Secretion reveals dynamics and spatial segregation of Salmonella effectors

  2010cites this paper
• Structural and functional implications of phosphorylation and acetylation in the regulation of the AAA+ protein p97.

  2010cites this paper
• Salmonella – the ultimate insider. Salmonella virulence factors that modulate intracellular survival

  2009cites this paper
• Bacterial Pathogenesis: Making a niche

  2009cites this paper
• New ATPase regulators--p97 goes to the PUB.

  2009cites this paper
• The FAM 104 proteins VCF 1 / 2 promote the nuclear localization of 1 p 97 / VCP 2 3 4

  year unknowncites this paper