Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system

Waterman, Scott R.; Holden, David W.

doi:10.1046/j.1462-5822.2003.00294.x

Cited by 349 publications

(289 citation statements)

References 81 publications

(172 reference statements)

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“…T3SS structural and effector genes require the ssrA/ssrB two-component system, which is also controlled by the PhoPQ system (Hensel et al, 1998;Waterman & Holden, 2003). To investigate a possible regulation of taiA and clyA by SsrB, we compared expression of these genes in the wild-type and in a DssrB isogenic strain, 24 h postinfection of human macrophages.…”

Section: Taia Is Secreted Independently Of Spi-1 or Spi-2 T3ssmentioning

confidence: 99%

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

2009

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Salmonella enterica serovar Typhi causes a human-restricted systemic infection called typhoid fever. We have identified a Typhi genomic region encoding two ORFs, STY1498 and STY1499, that are expressed during infection of human macrophages and organized in an operon. STY1498 corresponds to clyA, which encodes a pore-forming cytolysin, and STY1499 encodes a 27 kDa protein, without any attributed function, which we have named TaiA (Typhi-associated invasin A). In order to evaluate the roles of these genes in Typhi pathogenesis, isogenic Typhi strains harbouring a non-polar mutation of either clyA or taiA were constructed. In macrophages, taiA was involved in increasing phagocytosis, as taiA deletion reduced bacterial uptake, whereas clyA reduced or controlled bacterial growth, as clyA deletion enhanced Typhi survival within macrophages without affecting cytotoxicity. In epithelial cells, deletion of taiA had no effect on invasion, whereas deletion of clyA enhanced the Typhi invasion rate, and reduced cytotoxicity. Overexpression of taiA in Typhi or in Escherichia coli resulted in a higher invasion rate of epithelial cells. We have demonstrated that TaiA is secreted independently of both the Salmonella pathogenicity island (SPI)-1 and the SPI-2 type three secretion systems. We have shown that this operon is regulated by the virulence-associated regulator PhoP. Moreover, our results revealed that products of this operon might be involved in promoting the use of macrophages as a sheltered reservoir for Typhi and allowing long-term persistence inside the host. INTRODUCTIONThe genus Salmonella is composed of two distinct species, Salmonella bongori and Salmonella enterica. While S. bongori is rarely involved in human infections, S. enterica is a major human pathogen. Out of the 2000 serovars of S. enterica, only a small fraction is associated with human infections (Porwollik et al., 2004). Serovars Typhimurium and Enteritidis cause a localized infection, gastroenteritis, whereas serovar Typhi causes a severe systemic infection called typhoid fever, which kills an estimated 600 000 people annually (Parry et al., 2002). Because Typhi is restricted to humans, Typhimurium has been used for many years to study typhoid fever pathogenesis using a murine infection model in which Typhimurium causes a systemic infection. This model has been crucial in understanding systemic infections by Salmonella.S. enterica and S. bongori possess a type three secretion system (T3SS), encoded by Salmonella pathogenicity island 1 (SPI-1), which mediates invasion of host cells (Galan, 1999;Marcus et al., 2000). Only S. enterica possesses a second T3SS located in SPI-2, which is required for survival inside macrophages and the infection of mammalian hosts . The T3SS injects bacterial proteins directly into the host cell and disturbs normal cell function. Induction of the SPI-1-encoded genes requires high osmolarity and low aeration, conditions present in the small intestine where the SPI-1 T3SS initiates cell invasion (Altier, 2005;Lostroh & Lee,...

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Section: Taia Is Secreted Independently Of Spi-1 or Spi-2 T3ssmentioning

confidence: 99%

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

2009

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“…In addition, many virulence genes are clustered into coordinately regulated Salmonella pathogenicity islands (SPIs) (11). SPI1 genes are required for invasion by extracellular bacteria (12), and SPI2 genes encode one set of gene products required for intracellular replication and systemic infection (13). SPI1 and SPI2 genes are regulated in response to a variety of environmental signals including, but not limited to osmolarity (14 -16), pH (14,15,17), Mg 2ϩ depletion (7), oxygen tension (14), phosphate starvation (18), bile (19), cationic microbial peptides (20), and intestinal short-chain fatty acids (21).…”

Section: T He Pathogen Salmonella Enterica Serovar Typhimurium (Smentioning

confidence: 99%

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Cummings¹,

Barrett²,

Wilkerson³

et al. 2005

The Journal of Immunology

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Salmonella typhimurium, a facultatively intracellular pathogen, regulates expression of virulence factors in response to distinct environments encountered during the course of infection. We tested the hypothesis that the transition from extra- to intracellular environments during Salmonella infection triggers changes in Ag expression that impose both temporal and spatial limitations on the host T cell response. CD4+ T cells recovered from Salmonella immune mice were propagated in vitro using Ag derived from bacteria grown in conditions designed to emulate extra- or intracellular environments in vivo. Extracellular phase bacteria supported a dominant T cell response to the flagellar subunit protein FliC, whereas intracellular phase bacteria were unable to support expansion of FliC-specific T cells from populations known to contain T cells with reactivity to this Ag. This result was attributed to bacterial regulation of FliC expression: transcription and protein levels were repressed in bacteria growing in the spleens of infected mice. Furthermore, Salmonella-infected splenocytes taken directly ex vivo stimulated FliC-specific T cell clones only when intracellular FliC expression was artificially up-regulated. Although it has been suggested that a microanatomical separation of immune T cells and infected APC exists in vivo, we demonstrate that intracellular Salmonella can repress FliC expression below the T cell activation threshold. This potentially provides a mechanism for intracellular Salmonella at systemic sites to avoid detection by Ag-specific T cells primed at intestinal sites early in infection.

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“…This T3SS, encoded by the Salmonella pathogenicity island 1 (SPI-1), is a molecular syringe that injects bacterial effector proteins directly into host cells to manipulate host cell pathways, allowing bacterial invasion through a Trigger mechanism [4]. Another T3SS, encoded by the SPI-2, allows intracellular survival and multiplication of Salmonella within the vacuole [5].…”

Section: Introductionmentioning

confidence: 99%

Rck of Salmonella enterica, subspecies enterica serovar Enteritidis, mediates Zipper-like internalization

et al. 2010

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Salmonella can invade non-phagocytic cells through its type III secretion system (T3SS-1), which induces a Trigger entry process. This study showed that Salmonella enterica, subspecies enterica serovar Enteritidis can also invade cells via the Rck outer membrane protein. Rck was necessary and sufficient to enable non-invasive E. coli and Rckcoated beads to adhere to and invade different cells. Internalization analysis of latex beads coated with different Rck peptides showed that the peptide containing amino acids 140-150 promoted adhesion, whereas amino acids between 150 and 159 modulated invasion. Expression of dominant-negative derivatives and use of specific inhibitors demonstrated the crucial role of small GTPases Rac1 and Cdc42 in activating the Arp2/3 complex to trigger formation of actin-rich accumulation, leading to Rck-dependent internalization. Finally, scanning and transmission electron microscopy with Rck-coated beads and E. coli expressing Rck revealed microvillus-like extensions that formed a Zipper-like structure, engulfing the adherent beads and bacteria. Overall, our results provide new insights into the Salmonella T3SS-independent invasion mechanisms and strongly suggest that Rck induces a Zipper-like entry mechanism. Consequently, Salmonella seems to be the first bacterium found to be able to induce both Zipper and Trigger mechanisms to invade host cells.

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Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system

Cited by 349 publications

References 81 publications

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

FliC-Specific CD4+ T Cell Responses Are Restricted by Bacterial Regulation of Antigen Expression

Rck of Salmonella enterica, subspecies enterica serovar Enteritidis, mediates Zipper-like internalization

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