PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System

Phinet Name: Shigella spp.
Phinet Information
Pathogen Name: Shigella spp.
Pathogen NIAID Category: NIAID Category B
Bio-objects
Bio-object 1: Actin filaments depolymerization. Lamellipodial formation
GI Number: 145247787 Accession Number: Type: Pathway or action Location: Cytoplasm Description: IpaA-Vinculin structure results in very short actin filaments, indicating that the IpaA-Vinculin complex induces actin depolymerization and the Lamellipodial formation (<a href="#reference5478">Bourdet-Sicard et al., 1999</a>). WASP, N-WASP, and WIP play significant roles in the regulation of actin polymerisation, allowing the migration of cells and the movement of Shigella organisms. The activity and stability of WASP is regulated by WIP during the formation of actin-rich structures, including lamellipodia (<a href="#reference8681">AntÃ�Â³n et al., 2007</a>).
Bio-object 2: Endocytosis. Shiga Toxin (Subunit B) - membrane interaction
GI Number: 143770754 Accession Number: Type: Pathway or action Location: Cell membrane Function: Enzyme inhibitor Description: Following binding, toxin uptake occurs by various receptor-mediated endocytic pathways (<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>). Targeting properties of shiga toxins reside in their B subunit (<a href="#reference8682">TarragÃ�Â³-Trani and Storrie, 2007</a>).
Bio-object 3: Endoplasmic Reticulum. Shiga Toxin-Release of fragment A1(enzymatically active) from fragment A2
GI Number: 16120353 Accession Number: Type: Pathway or action Location: Cell membrane Function: Enzyme Description: The A1 enzymatically active part is released from the A2 fragment in the ER (<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>).
Bio-object 4: Escape of Shigella from the vacuole into the cytoplasm
GI Number: 145259569 Accession Number: Type: Pathway or action Location: Cytoplasm Description: Lysis of the vacuolar membrane allows escape of Shigella into the cytoplasm of the newly infected cells (<a href="#reference5480">Fernandez et al., 2001</a>).
Bio-object 5: Expression of IcsA protein on Shigella surface
GI Number: 13448939 Accession Number: Type: Pathway or action Location: Bacterial membrane or virus envelope Description: IcsA protein is exported into the bacterial outer membrane and required to induce actin polymerization.(<a href="#reference5480">Fernandez et al., 2001</a>)(<a href="#reference5481">Magdalena et al., 2002</a>)
Bio-object 6: Furin
GI Number: 20336193 Accession Number: Type: Protein or gene Location: Cytoplasm Function: Enzyme Description: Furin is a critical enzyme for the processing of Shiga toxin (cleavage of Shiga toxin)(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 7: Golgi Apparatus. Shiga Toxin-Subunit A nicking by protease Furin
GI Number: 145250049 Accession Number: Type: Pathway or action Location: Cell membrane Function: Enzyme Description: Followed by transport to the Golgi apparatus and endoplasmic reticulum (ER), the A subunit is cleaved by furin in the endosomes/Golgi apparatus (<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>).
Bio-object 8: Inhibition of binding of aminoacyl - tRNA
GI Number: 30061571 Accession Number: Type: Pathway or action Location: Organelle -- Ribosome Function: Nucleic acid binding Description: Inhibition of binding of aminoacyl-tRNA to the 60S ribosomal subunit (<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>).
Bio-object 9: IpaA translocation via TTSS-Mxi-Ipa structure
GI Number: 31983523 Accession Number: Type: Pathway or action Location: Cytoplasm Description: IpaA is injected into the host cell cytosol (<a href="#reference5478">Bourdet-Sicard et al., 1999</a>). The needle component of the type III secreton (TTSS) of Shigella regulates the activity of the secretion apparatus, which serves to transfer bacterial proteins into host cells. IpaA and IpgD, two supplementary effectors of cell invasion, are transferred into the host cytoplasm. TTSS activation requires direct contact of the external distal tip of the apparatus with the host cell. The monomeric unit of the Shigella flexneri needle, MxiH, forms a superhelical assembly. The needle directly controls the activity of the TTSS and suggest that it may be used to "sense" host cells (<a href="#reference8683">Kenjale et al., 2005</a>).
Bio-object 10: IpaA-Vinculin complex formation
GI Number: 2642477 Accession Number: DB Links: dbGSS Id: 1179795 GSS name: U97493 Type: Protein or gene complex Location: Cytoplasm Description: This process results from the binding of IpaA to vinculin (a cytoskeleton-associated protein) (<a href="#reference5478">Bourdet-Sicard et al., 1999</a>). Vinculin links integrin receptors to the actin cytoskeleton by binding to talin, is held in an inactive closed-clamp conformation through hydrophobic interactions between its head and tail domains, and activation depends on severing this interaction by talin and IpaA and allowing vinculin to bind to its other partners. The lower affinity VBS of IpaA can also bind to the adjacent C-terminal four-helical bundle of vinculin's head domain through a helix addition mechanism. These hydrophobic interactions do not alter the conformation of this helical bundle, and the architecture of the complex suggests that IpaA can simultaneously interact with both of the four-helical bundle domains of vinculin's N-terminus to stabilize vinculin-IpaA interactions (<a href="#reference8684">Nhieu and Izard, 2007</a>). Upon bacterial-cell contact, the type III bacterial effector IpaA binds to the cytoskeletal protein vinculin to promote actin reorganization required for efficient bacterial uptake. The last 74 C-terminal residues of IpaA bind to vinculin and promotes its association with actin filaments. IpaA regulates actin polymerisation/depolymerisation at sites of Shigella invasion by modulating the barbed end capping activity of vinculin (<a href="#reference8685">Ramarao et al., 2007</a>). IpaA is injected into the epithelial cell by a TTSS and recruits vinculin to regulate actin polymerization at the site of entry. IpaA has two vinculin-binding sites that simultaneously bind two VD1 molecules. The interaction of IpaA with VD1 is highly similar to the interaction of the endogenous, eukaryotic proteins talin and alpha-actinin with VD1, showing that Shigella uses a structural mimicry strategy to activate vinculin (<a href="#reference8686">Hamiaux et al., 2006</a>).
Bio-object 11: IpaB and IpaC disrupt the vacuolar membrane
Type: Pathway or action Location: Cell membrane Description: IpaB and IpaC complex induces the membrane lysis.(<a href="#reference5480">Fernandez et al., 2001</a>)
Bio-object 12: IpaB, IpaC, IpaD translocation via TTSS-MxiH-MxiI (TTSS-Mxi) complex
Type: Pathway or action Location: Extracellular Function: Transporter Description: IpaB, C, D proteins are translocated directly into the host plasma membrane and associated with infected host cell membrane.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Bio-object 13: IpaB-IpaC complex formation
Type: Protein or gene complex Location: Cell membrane Function: Transporter Description: IpaB and IpaC form a complex which inserts into the host cell membrane.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Bio-object 14: IpaB-IpaD complex. Control proteins flux
Type: Protein or gene complex Location: Cell membrane Function: Transporter Description: This complex controls the flux of proteins through the type III secreton systems.(<a href="#reference5477">De et al., 2000</a>)
Bio-object 15: IpaC modulates Cdc 42-dependent Filopodial formation
Type: Pathway or action Location: Cytoplasm Description: Shigella cells form filopodial structures that eventually give rise to lamellipodial structure. The mechanisms involved in the activation of Cdc42 and Rac by IpaC are currently unknown.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Bio-object 16: IpaC modulates Rac1-dependent Lamellipodial formation
Type: Pathway or action Location: Cytoplasm Description: Shigella cells form filopodial structures that eventually give rise to lamellipodial structure. The mechanisms involved in the activation of Cdc42 and Rac by IpaC are currently unknown.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Bio-object 17: Movement within the cytoplasm is mediated by IcsA
Type: Pathway or action Location: Cytoplasm Description: Movement within the cytoplasm is mediated by IcsA protein. IcsA is essential for proper assembly of the comet tail and movement inside the cell cytoplasm.(<a href="#reference5481">Magdalena et al., 2002</a>)(<a href="#reference5482">Monack et al., 2001</a>)
Bio-object 18: MxiH, MxiI secretion via TTSS. MxiH-MxiI structure formation
Type: Pathway or action Location: Bacterial membrane or virus envelope Function: Transporter Description: MxiH (Membrane Expression of Invasion), MxiI proteins are secreted via the type III secretion apparatus.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Bio-object 19: Protein synthesis blocking and death of intoxicated cells
Type: Pathway or action Location: Cytoplasm Description: This action blocks protein synthesis, resulting in death of intoxicated cells. The B subunit is capable of triggering apoptosis, mechanism not understood(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 20: Ribosome. The A1 fragment cleaves the N-glycosidic bond in 28S rRNA
Type: Pathway or action Location: Organelle -- Ribosome Function: Nucleic acid binding Description: The A1 fragment cleaves the N-glycosidic bond, removing one adenine from adenosine in position 4324 from the 5' terminus in 28S rRNA of the 60S ribosomal subunit(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 21: Shiga Toxin realease ( Subunit A - Subunit B (pentameric ring))
Type: Pathway or action Location: Extracellular Function: Enzyme inhibitor Description: The Shiga toxin is composed of a single catalytic subunit A that is associated with a pentameric ring formed by subunit B(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 22: Shiga Toxin secretion by bacterial cells
Type: Pathway or action Location: Bacterial membrane or virus envelope Function: Transporter Description: Shiga Toxin secretion by bacterial cells(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 23: Shigella induction of apoptosis
Type: Pathway or action Location: Cytoplasm Description: Essential events in the pathogenesis of Shigella infection result in induction of apoptosis in macrophages.(<a href="#reference5483">Guichon et al., 2001</a>)
Bio-object 24: Shigella internalization in vacuole
Type: Pathway or action Location: Phagosome Description: This process induces and modulates the macropinocytic vacuole.(<a href="#reference5479">Tran et al., 1999</a>)(<a href="#reference5480">Fernandez et al., 2001</a>)
Bio-object 25: Shigella intracellular and intercellular spread
Type: Pathway or action Location: Cytoplasm Description: IcsA achieves the actin-based motility of Shigella and permits its passage from one cell to another. Actin-based motility allows cell-to-cell spread in a process that involves the cellular junction.(<a href="#reference5482">Monack et al., 2001</a>)
Bio-object 26: Shigella-induced cytoskeletal rearrangements
Type: Pathway or action Location: Cytoplasm Description: This results in a macropinocytic pocket which engulfs the microorganism.(<a href="#reference5479">Tran et al., 1999</a>)
Bio-object 27: Subunit B - Receptor Gb3 interaction on host cell surface (Gb3 - Globotiaosyl ceramide)
Type: Microbe-host cell complex Location: Cell membrane Function: Enzyme inhibitor Description: The B subunit binds globotriaosyl ceramide (Gb3) glycolipid receptor on cell surfaces(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 28: Trans-Golgi Network. Shiga Toxin-Subunit A nicking by protease Furin
Type: Pathway or action Location: Cell membrane Function: Enzyme Description: Followed by transport to the Trans-Golgi Network and endoplasmic reticulum (ER), the A subunit is cleaved by furin in the Trans-Golgi Network(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Bio-object 29: TTSS-MxiH(n), TTSS-MxiI(n). Needle like structure formation
Type: Protein or gene complex Location: Extracellular Function: Transporter Description: Mxi proteins form an extension on the bacterial surface enabling the transfer of the Ipa proteins (Invasion Plasmid Antigen) directly into the host cell.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Bio-object 30: TTSS-MxiH-MxiI-IpaB-IpaD (TTSS-Mxi-Ipa) structure formation
Type: Protein or gene complex Location: Cell membrane Function: Transporter Description: This structure controls the translocation of proteins through the type III secretion apparatus.(<a href="#reference5477">De et al., 2000</a>)
Bio-object 31: Type III Secretion System
Type: Pathway or action Location: Bacterial membrane or virus envelope Function: Transporter Description: Shigella virulence proteins are secreted via the type III secretion apparatus (TTSS) across the envelope.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Bio-object 32: Vesicles containing Shiga Toxin. Shiga Toxin transport to the Trans-Golgi Network
Type: Pathway or action Location: Cell membrane Function: Enzyme inhibitor Description: Endosomes are transported to the Trans-Golgi Network (TGN)(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interactions
Interaction 1: Interaction1
Input Objects: Shiga Toxin secretion by bacterial cells Output Objects: Shiga Toxin realease ( Subunit A - Subunit B (pentameric ring)) GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin secretion. Subunit A - Subunit B (pentameric ring).(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 2: Interaction2
Input Objects: Shiga Toxin realease ( Subunit A - Subunit B (pentameric ring)) Output Objects: Subunit B - Receptor Gb3 interaction on host cell surface (Gb3 - Globotiaosyl ceramide) GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin Receptor Gb3 (Globotiaosyl ceramide) interaction on host cell surface.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 3: Interaction3
Input Objects: Subunit B - Receptor Gb3 interaction on host cell surface (Gb3 - Globotiaosyl ceramide) Output Objects: Endocytosis. Shiga Toxin (Subunit B) - membrane interaction GO Evidence Code: Inferred from Direct Assay Description: Endocytosis. Shiga Toxin - membrane interaction.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 4: Interaction4
Input Objects: Endocytosis. Shiga Toxin (Subunit B) - membrane interaction Output Objects: Vesicles containing Shiga Toxin. Shiga Toxin transport to the Trans-Golgi Network GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin transport to the Trans-Golgi Network.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 5: Interaction5
Cofactors: Furin Input Objects: Vesicles containing Shiga Toxin. Shiga Toxin transport to the Trans-Golgi Network Output Objects: Trans-Golgi Network. Shiga Toxin-Subunit A nicking by protease Furin GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin. Subunit A nicking by protease Furin.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 6: Interaction6
Cofactors: Furin Input Objects: Trans-Golgi Network. Shiga Toxin-Subunit A nicking by protease Furin Output Objects: Golgi Apparatus. Shiga Toxin-Subunit A nicking by protease Furin GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin Subunit A nicking by protease Furin.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 7: Interaction7
Input Objects: Golgi Apparatus. Shiga Toxin-Subunit A nicking by protease Furin Output Objects: Endoplasmic Reticulum. Shiga Toxin-Release of fragment A1(enzymatically active) from fragment A2 GO Evidence Code: Inferred from Direct Assay Description: The Shiga Toxin. Release of fragment A1.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 8: Interaction8
Input Objects: Endoplasmic Reticulum. Shiga Toxin-Release of fragment A1(enzymatically active) from fragment A2 Output Objects: Ribosome. The A1 fragment cleaves the N-glycosidic bond in 28S rRNA GO Evidence Code: Inferred from Direct Assay Description: The A1 fragment cleaves the 28S rRNA.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 9: Interaction9
Input Objects: Ribosome. The A1 fragment cleaves the N-glycosidic bond in 28S rRNA Output Objects: Inhibition of binding of aminoacyl - tRNA GO Evidence Code: Inferred from Direct Assay Description: Inhibition of binding of aminoacyl-tRNA to the ribosomal subunit.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 10: Interaction10
Input Objects: Inhibition of binding of aminoacyl - tRNA Output Objects: Protein synthesis blocking and death of intoxicated cells GO Evidence Code: Inferred from Direct Assay Description: The B subunit is capable of triggering apoptosis.(<a href="#reference5471">Sandvig, 2001</a>)(<a href="#reference5472">Sandvig et al., 1996</a>)(<a href="#reference5473">Garred et al., 1997</a>)
Interaction 11: Interaction11
Input Objects: Type III Secretion System Output Objects: MxiH, MxiI secretion via TTSS. MxiH-MxiI structure formation GO Evidence Code: Inferred from Direct Assay Description: Shigella virulence proteins (MxiH, MxiI) secretion via the type III secretion system (TTSS). MxiH-MxiI structure formation.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Interaction 12: Interaction12
Input Objects: MxiH, MxiI secretion via TTSS. MxiH-MxiI structure formation Output Objects: TTSS-MxiH(n), TTSS-MxiI(n). Needle like structure formation GO Evidence Code: Inferred from Direct Assay Description: TTSS-MxiH-MxiI interaction. Needle like structure formation.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Interaction 13: Interaction13
Input Objects: TTSS-MxiH(n), TTSS-MxiI(n). Needle like structure formation Output Objects: IpaB, IpaC, IpaD translocation via TTSS-MxiH-MxiI (TTSS-Mxi) complex GO Evidence Code: Inferred from Direct Assay Description: IpaB, C, D proteins secretion directly into the host plasma membrane.(<a href="#reference5474">Bahrani et al., 1997</a>)(<a href="#reference5475">Magdalena et al., 2002</a>)(<a href="#reference5476">Blocker et al., 1999</a>)
Interaction 14: Interaction14
Input Objects: IpaB, IpaC, IpaD translocation via TTSS-MxiH-MxiI (TTSS-Mxi) complex Output Objects: TTSS-MxiH-MxiI-IpaB-IpaD (TTSS-Mxi-Ipa) structure formation GO Evidence Code: Inferred from Direct Assay Description: TTSS-MxiH-MxiI-IpaB-IpaD (TTSS-Mxi-Ipa) structure controls the translocation of proteins through TTSS.(<a href="#reference5477">De et al., 2000</a>)
Interaction 15: Interaction15
Input Objects: TTSS-MxiH-MxiI-IpaB-IpaD (TTSS-Mxi-Ipa) structure formation Output Objects: IpaB-IpaD complex. Control proteins flux, IpaB-IpaC complex formation GO Evidence Code: Inferred from Direct Assay Description: IpaB-IpaD complex and IpaB-IpaC complex formation. These complexes insert into the host cell membrane and control the flux of proteins through TTSS.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Interaction 16: Interaction16
Input Objects: IpaB-IpaC complex formation Output Objects: IpaC modulates Cdc 42-dependent Filopodial formation, IpaC modulates Rac1-dependent Lamellipodial formation, IpaA translocation via TTSS-Mxi-Ipa structure GO Evidence Code: Inferred from Direct Assay Description: Shigella cells form filopodial structures that eventually lead to lamellipodial structure formation. IpaA injection into the host cell cytosol.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5478">Bourdet-Sicard et al., 1999</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Interaction 17: Interaction17
Input Objects: IpaA translocation via TTSS-Mxi-Ipa structure Output Objects: IpaA-Vinculin complex formation GO Evidence Code: Inferred from Direct Assay Description: The IpaA binding to the host cytoskeleton-associated protein vinculin.(<a href="#reference5478">Bourdet-Sicard et al., 1999</a>)
Interaction 18: Interaction18
Input Objects: IpaA-Vinculin complex formation Output Objects: Actin filaments depolymerization. Lamellipodial formation GO Evidence Code: Inferred from Direct Assay Description: The IpaA-Vinculin complex induces actin depolymerization and lamellipodial formation.(<a href="#reference5478">Bourdet-Sicard et al., 1999</a>)
Interaction 19: Interaction19
Input Objects: Actin filaments depolymerization. Lamellipodial formation Output Objects: Shigella-induced cytoskeletal rearrangements GO Evidence Code: Inferred from Direct Assay Description: The host cytoskeletal rearrangements.(<a href="#reference5479">Tran et al., 1999</a>)
Interaction 20: Interaction20
Input Objects: Shigella-induced cytoskeletal rearrangements Output Objects: Shigella internalization in vacuole GO Evidence Code: Inferred from Direct Assay Description: The formation of the Shigella containing macropinocytic vacuole.(<a href="#reference5479">Tran et al., 1999</a>)(<a href="#reference5480">Fernandez et al., 2001</a>)
Interaction 21: Interaction21
Input Objects: Shigella internalization in vacuole Output Objects: IpaB and IpaC disrupt the vacuolar membrane GO Evidence Code: Inferred from Direct Assay Description: The host vacuolar membrane lysis by the IpaB and IpaC complex.(<a href="#reference5480">Fernandez et al., 2001</a>)
Interaction 22: Interaction22
Input Objects: IpaB and IpaC disrupt the vacuolar membrane Output Objects: Escape of Shigella from the vacuole into the cytoplasm GO Evidence Code: Inferred from Direct Assay Description: Lysis of the vacuolar membrane releases of Shigella cells into the cytoplasm of the infected cells.(<a href="#reference5480">Fernandez et al., 2001</a>)
Interaction 23: Interaction23
Input Objects: Escape of Shigella from the vacuole into the cytoplasm Output Objects: Expression of IcsA protein on Shigella surface GO Evidence Code: Inferred from Direct Assay Description: Export and expression of IcsA protein on Shigella cell surface.(<a href="#reference5480">Fernandez et al., 2001</a>)(<a href="#reference5481">Magdalena et al., 2002</a>)
Interaction 24: Interaction24
Input Objects: Expression of IcsA protein on Shigella surface Output Objects: Movement within the cytoplasm is mediated by IcsA GO Evidence Code: Inferred from Direct Assay Description: IcsA is essential for assembly of the comet tail and Shigella cell movement inside the host cell cytoplasm.(<a href="#reference5481">Magdalena et al., 2002</a>)(<a href="#reference5482">Monack et al., 2001</a>)
Interaction 25: Interaction25
Input Objects: Movement within the cytoplasm is mediated by IcsA Output Objects: Shigella intracellular and intercellular spread GO Evidence Code: Inferred from Direct Assay Description: Actin-based motility activates cell-to-cell spread of Shigella cells in a process that involves the cellular junction.(<a href="#reference5482">Monack et al., 2001</a>)
Interaction 26: Interaction26
Input Objects: Shigella intracellular and intercellular spread Output Objects: Shigella induction of apoptosis GO Evidence Code: Inferred from Direct Assay Description: Shigella induction of apoptosis in macrophages.(<a href="#reference5483">Guichon et al., 2001</a>)
Interaction 27: Interaction27
Input Objects: IpaC modulates Cdc 42-dependent Filopodial formation, IpaC modulates Rac1-dependent Lamellipodial formation Output Objects: Shigella-induced cytoskeletal rearrangements GO Evidence Code: Inferred from Direct Assay Description: Shigella cells form filopodial structures that eventually lead to lamellipodial structure formation and host cytoskeletal rearrangements.(<a href="#reference5477">De et al., 2000</a>)(<a href="#reference5479">Tran et al., 1999</a>)
Pathways

Phinet Name: Shigella spp.