SseK1 and SseK2 Are Novel Translocated Proteins of<i>Salmonella enterica</i>Serovar Typhimurium

Choy, Sonya L. Kujat; Boyle, Erin C.; Gal-Mor, Ohad; Goode, David; Valdez, Yanet; Vallance, Bruce A.; Finlay, B. Brett

doi:10.1128/iai.72.9.5115-5125.2004

Cited by 72 publications

(76 citation statements)

References 62 publications

(50 reference statements)

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“…3R, S). In BALB/c mice, deletion of sseK2 did not have any effect on virulence [51]. Other researchers found a small effect of the sseK family on virulence but observed no effect by deleting sseK3 alone [73].…”

Section: Resultsmentioning

confidence: 87%

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Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

et al. 2013

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Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and is a model of typhoid fever in humans. One of the hallmarks of typhoid is persistence, the ability of the bacteria to survive in the host weeks after infection. Virulence factors called effectors facilitate this process by direct transfer to the cytoplasm of infected cells thereby subverting cellular processes. Secretion of effectors to the cell cytoplasm takes place through multiple routes, including two separate type III secretion (T3SS) apparati as well as outer membrane vesicles. The two T3SS are encoded on separate pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are required for persistence, but the effectors required have not been systematically evaluated. In this study, mutations in 48 described effectors were tested for persistence. We replaced each effector with a specific DNA barcode sequence by allelic exchange and co-infected with a wild-type reference to calculate the ratio of wild-type parent to mutant at different times after infection. The competitive index (CI) was determined by quantitative PCR in which primers that correspond to the barcode were used for amplification. Mutations in all but seven effectors reduced persistence demonstrating that most effectors were required. One exception was CigR, a recently discovered effector that is widely conserved throughout enteric bacteria. Deletion of cigR increased lethality, suggesting that it may be an anti-virulence factor. The fact that almost all Salmonella effectors are required for persistence argues against redundant functions. This is different from effector repertoires in other intracellular pathogens such as Legionella.

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Section: Resultsmentioning

confidence: 87%

“…2G). It has been demonstrated that after translocation, SseK1 localizes to the host cytosol, which is uncommon for Salmonella effectors [51]. SspH1 contains leucine-rich repeats that interact with mitogen activated protein kinase 1 [52].…”

Section: Resultsmentioning

confidence: 99%

Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

et al. 2013

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“…Previous work on SseK1 and 2 failed to find a role in virulence, either in terms of replication of Salmonella inside host cells or virulence in mice [12]. Considering that this could be due to functional redundancy with SseK3, which was functional in the strains tested by Kujat Choy et al [12], we initially focussed our efforts in studying a strain mutated for all three SseK family members.…”

Section: Resultsmentioning

confidence: 99%

“…Considering that this could be due to functional redundancy with SseK3, which was functional in the strains tested by Kujat Choy et al [12], we initially focussed our efforts in studying a strain mutated for all three SseK family members. Whilst we found no phenotype for the SseK family during intracellular replication in RAW264.7 cells (data not shown) we did identify a statistically significant ( P <0.0001) attenuation at 72 h post-inoculation using competitive index infections of mice.…”

Section: Resultsmentioning

confidence: 99%

Salmonella Phage ST64B Encodes a Member of the SseK/NleB Effector Family

et al. 2011

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Salmonella enterica is a species of bacteria that is a major cause of enteritis across the globe, while certain serovars cause typhoid, a more serious disease associated with a significant mortality rate. Type III secreted effectors are major contributors to the pathogenesis of Salmonella infections. Genes encoding effectors are acquired via horizontal gene transfer, and a subset are encoded within active phage lysogens. Because the acquisition of effectors is in flux, the complement of effectors possessed by various Salmonella strains frequently differs. By comparing the genome sequences of S. enterica serovar Typhimurium strain SL1344 with LT2, we identified a gene with significant similarity to SseK/NleB type III secreted effector proteins within a phage ST64B lysogen that is absent from LT2. We have named this gene sseK3. SseK3 was co-regulated with the SPI-2 type III secretion system in vitro and inside host cells, and was also injected into infected host cells. While no role for SseK3 in virulence could be identified, a role for the other family members in murine typhoid was found. SseK3 and other phage-encoded effectors were found to have a significant but sparse distribution in the available Salmonella genome sequences, indicating the potential for more uncharacterised effectors to be present in less studied serovars. These phage-encoded effectors may be principle subjects of contemporary selective processes shaping Salmonella-host interactions.

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“…Interestingly, STM2137 (also known as SseK2) is a likely paralog of SseK1, an effector translocated by the SPI-2 T3SS [33]. SseK2 is also regulated by the SsrA-SsrB two-component system but compared to SseK1, it is translocated in much less abundance into host cells [33].…”

Section: Discussionmentioning

confidence: 99%

Structural and Biochemical Characterization of SrcA, a Multi-Cargo Type III Secretion Chaperone in Salmonella Required for Pathogenic Association with a Host

et al. 2010

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Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2) is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 Å revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.

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SseK1 and SseK2 Are Novel Translocated Proteins ofSalmonella entericaSerovar Typhimurium

Cited by 72 publications

References 62 publications

Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

Diverse Secreted Effectors Are Required for Salmonella Persistence in a Mouse Infection Model

Salmonella Phage ST64B Encodes a Member of the SseK/NleB Effector Family

Structural and Biochemical Characterization of SrcA, a Multi-Cargo Type III Secretion Chaperone in Salmonella Required for Pathogenic Association with a Host

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