The Salmonella Effector SseK3 Targets Small Rab GTPases
During infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00419/full |
| _version_ | 1818457468804530176 |
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| author | Jiyao Gan Jiyao Gan Nichollas E. Scott Joshua P. M. Newson Rachelia R. Wibawa Rachelia R. Wibawa Tania Wong Fok Lung Georgina L. Pollock Garrett Z. Ng Ian van Driel Jaclyn S. Pearson Jaclyn S. Pearson Elizabeth L. Hartland Elizabeth L. Hartland Cristina Giogha Cristina Giogha |
| author_facet | Jiyao Gan Jiyao Gan Nichollas E. Scott Joshua P. M. Newson Rachelia R. Wibawa Rachelia R. Wibawa Tania Wong Fok Lung Georgina L. Pollock Garrett Z. Ng Ian van Driel Jaclyn S. Pearson Jaclyn S. Pearson Elizabeth L. Hartland Elizabeth L. Hartland Cristina Giogha Cristina Giogha |
| author_sort | Jiyao Gan |
| collection | DOAJ |
| description | During infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish the Salmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages of Salmonella infection by SseK3, an arginine N-acetylglucosamine (GlcNAc) transferase effector translocated via the Salmonella pathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute to Salmonella infection by interfering with the activity of key Rab GTPases. |
| first_indexed | 2024-12-14T22:43:03Z |
| format | Article |
| id | doaj.art-8dfb7361296d425e9817e655b46d95ba |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-14T22:43:03Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-8dfb7361296d425e9817e655b46d95ba2022-12-21T22:44:56ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-08-011010.3389/fcimb.2020.00419549696The Salmonella Effector SseK3 Targets Small Rab GTPasesJiyao Gan0Jiyao Gan1Nichollas E. Scott2Joshua P. M. Newson3Rachelia R. Wibawa4Rachelia R. Wibawa5Tania Wong Fok Lung6Georgina L. Pollock7Garrett Z. Ng8Ian van Driel9Jaclyn S. Pearson10Jaclyn S. Pearson11Elizabeth L. Hartland12Elizabeth L. Hartland13Cristina Giogha14Cristina Giogha15Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Molecular and Translational Science, Monash University, Clayton, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Molecular and Translational Science, Monash University, Clayton, VIC, AustraliaCentre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, AustraliaDepartment of Molecular and Translational Science, Monash University, Clayton, VIC, AustraliaDuring infection, Salmonella species inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection, Salmonella exploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish the Salmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages of Salmonella infection by SseK3, an arginine N-acetylglucosamine (GlcNAc) transferase effector translocated via the Salmonella pathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute to Salmonella infection by interfering with the activity of key Rab GTPases.https://www.frontiersin.org/article/10.3389/fcimb.2020.00419/fullSalmonella entericaRabglycosyltransferaseprotein secretionhost-pathogen interaction |
| spellingShingle | Jiyao Gan Jiyao Gan Nichollas E. Scott Joshua P. M. Newson Rachelia R. Wibawa Rachelia R. Wibawa Tania Wong Fok Lung Georgina L. Pollock Garrett Z. Ng Ian van Driel Jaclyn S. Pearson Jaclyn S. Pearson Elizabeth L. Hartland Elizabeth L. Hartland Cristina Giogha Cristina Giogha The Salmonella Effector SseK3 Targets Small Rab GTPases Frontiers in Cellular and Infection Microbiology Salmonella enterica Rab glycosyltransferase protein secretion host-pathogen interaction |
| title | The Salmonella Effector SseK3 Targets Small Rab GTPases |
| title_full | The Salmonella Effector SseK3 Targets Small Rab GTPases |
| title_fullStr | The Salmonella Effector SseK3 Targets Small Rab GTPases |
| title_full_unstemmed | The Salmonella Effector SseK3 Targets Small Rab GTPases |
| title_short | The Salmonella Effector SseK3 Targets Small Rab GTPases |
| title_sort | salmonella effector ssek3 targets small rab gtpases |
| topic | Salmonella enterica Rab glycosyltransferase protein secretion host-pathogen interaction |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00419/full |
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