<i>Salmonella typhimurium</i> leucine‐rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems

Miao, Edward A.; Scherer, Christina; Tsolis, Renée M.; Kingsley, Robert A.; Adams, L. Garry; Bäumler, Andreas J.; Miller, Samuel I.

doi:10.1046/j.1365-2958.1999.01651.x

Cited by 258 publications

(328 citation statements)

References 63 publications

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“…We used the bacterial species S. bongori and E. coli Mutaflor as heterologous hosts in the present study. We observed that various virulence factors of S. enterica are absent in S. bongori, most importantly the SPI2 locus (20,34) and various loci encoding effector proteins of the SPI2-encoded T3SS (16,24,31). Mutaflor is an E. coli strain that is nonpathogenic but, in contrast to common lab strains, fully capable of colonizing the intestine.…”

Section: Resultsmentioning

confidence: 97%

“…There are also the translocated effector proteins SseF and SseG encoded within the SPI2 locus that colocalize with the endosomal membrane compartments after translocation by intracellular Salmonella (25). All of the SPI2-specific effector proteins currently known are absent in S. bongori (16,24,31). The total number of genes encoding translocated effectors is not known, and the function of the identified effector proteins is only partially understood.…”

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Functional Transfer of Salmonella Pathogenicity Island 2 to Salmonella bongori and Escherichia coli

2004

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The type III secretion system (T3SS) encoded by the Salmonella pathogenicity island 2 (SPI2) has a central role in systemic infections by Salmonella enterica and for the intracellular phenotype. Intracellular S. enterica uses the SPI2-encoded T3SS to translocate a set of effector proteins into the host cell, which modify host cell functions, enabling intracellular survival and replication of the bacteria. We sought to determine whether specific functions of the SPI2-encoded T3SS can be transferred to heterologous hosts Salmonella bongori and Escherichia coli Mutaflor, species that lack the SPI2 locus and loci encoding effector proteins. The SPI2 virulence locus was cloned and functionally expressed in S. bongori and E. coli. Here, we demonstrate that S. bongori harboring the SPI2 locus is capable of secretion of SPI2 substrate proteins under culture conditions, as well as of translocation of effector proteins under intracellular conditions. An SPI2-mediated cellular phenotype was induced by S. bongori harboring the SPI2 if the sifA locus was cotransferred. An interference with the host cell microtubule cytoskeleton, a novel SPI2-dependent phenotype, was observed in epithelial cells infected with S. bongori harboring SPI2 without additional effector genes. S. bongori harboring SPI2 showed increased intracellular persistence in a cell culture model, but SPI2 transfer was not sufficient to confer to S. bongori systemic pathogenicity in a murine model. Transfer of SPI2 to heterologous hosts offers a new tool for the study of SPI2 functions and the phenotypes of individual effectors.During the evolution of bacterial pathogenesis, the horizontal transfer of virulence genes has been a driving force for the emergence of new species and the adaptation of pathogens to new hosts and specific sites in these hosts. It has been concluded that large clusters of virulence genes are exchanged between various bacteria, and the acquisitions of so-called "pathogenicity islands" are considered as quantum leaps in the evolution of bacterial pathogenesis (13,35).Salmonella spp. form a complex group of gastrointestinal pathogens of animals and humans. Traditionally, a large number of isolates of Salmonella enterica have been defined as species due to distinct serological differences. However, molecular analyses indicated that most of these isolates represent serotypes of the species S. enterica, for example, S. enterica subspecies I serotype Typhimurium, and current taxonomy defines two species of Salmonella. Human infections are most frequently caused by various serovars of S. enterica. Disease outcomes associated with S. enterica can range from self-limiting localized gastrointestinal infections to life-threatening systemic infections such as typhoid fever (9). S. bongori, a second Salmonella species, is only rarely observed in human infections and is found as a commensal of cold-blooded animals (4, 38). Molecular analyses indicated that S. bongori represents a phylogenetically older separation from the genus Salmonella (4, 6).Beside...

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Section: Resultsmentioning

confidence: 97%

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Functional Transfer of Salmonella Pathogenicity Island 2 to Salmonella bongori and Escherichia coli

2004

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“…It is common that a bacterial pathogen codes for numerous effectors but the presence of multiple paralogs of a specific translocated effector in the same organism is only occasionally found (28)(29)(30). The close similarity among proteins in a family points to functional redundancy, which may provide an explanation for the failure to identify these proteins in previous genetic screens for bacterial mutants defective in intracellular growth.…”

Section: Discussionmentioning

confidence: 99%

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Luo

Isberg

2004

Proc. Natl. Acad. Sci. U.S.A.

466

549

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Legionella pneumophila is an intracellular pathogen that multiplies in a specialized vacuole within host cells. Biogenesis of this vacuole requires the Dot͞Icm type IV protein translocation system. By using a Cre͞loxP-based protein translocation assay, we found that proteins translocated by the Dot͞Icm complex across the host phagosomal membrane can also be transferred from one bacterial cell to another. The flexibility of this system allowed the identification of several families of proteins translocated by the Dot͞Icm complex. When analyzed by immunofluorescence microscopy, a protein identified by this procedure, SidC, was shown to translocate across the phagosomal membranes to the cytoplasmic face of the L. pneumophila phagosome. The identification of large numbers of these substrates, and the fact that the absence of any one substrate rarely results in strong defects in intracellular growth, indicate that there is significant functional redundancy among the Dot͞Icm translocation targets.bacterial pathogenesis ͉ protein translocation ͉ plasmid conjugation A ctive modification of host cellular functions is essential for a bacterial pathogen to establish a successful infection. Such modification often is mediated by injecting effectors into the host cytoplasm through specialized protein secretion systems (1). Among these systems, conjugation-adaptive transporters, also called type IV secretion systems (TFSS), have been identified in a number of bacterial pathogens (2). Many of these TFSS are dedicated DNA transfer apparatuses, whereas others allow Gram-negative bacterial pathogens to translocate protein substrates directly into the cytosol of eukaryotic cells. Only a few protein substrates of TFSS that are translocated into host cells have been identified (2).Legionella pneumophila is an intracellular pathogen that causes Legionnaire's disease. After being phagocytosed by macrophages, the bacteria multiply within a specialized vacuole that is initially isolated from the endocytic pathway (3, 4), possibly by intercepting early secretory vesicles (5). Biogenesis of this replicative phagosome requires the TFSS transporter called Dot͞ Icm (6, 7). Substrates transported by this apparatus are believed to directly promote the targeting pathway of the bacterial vacuole (8). Two of these substrates, RalF and LidA, have been identified (9, 10). RalF is a guanine nucleotide exchange factor for multiple Arf proteins (9), whereas the biochemical activity of LidA is unknown (10). There are clearly other unidentified substrates of Dot͞Icm, as mutations that specifically eliminate LidA cause negligible defects in intracellular growth and mutations in ralF are proficient for intracellular replication (9, 10). A comprehensive analysis of the identity and function of effectors translocated by the Dot͞Icm apparatus is crucial in determining how this bacterium establishes a replication vacuole. We report here that proteins translocated from bacteria to host cells can also be transferred between bacterial cells, allowing identificat...

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“…Some of these effectors engage and manipulate the host actin cytoskeleton machinery to facilitate bacterial internalization into host cells (3,(7)(8)(9)(10)(11). The translocation of these effectors through the host plasma membrane requires Salmonella SipB, SipC, and SipD (12)(13)(14)(15)(16).…”

Section: Salmonella Enterica Serovar Typhimurium (S Typhimurium)mentioning

confidence: 99%

The C Terminus of SipC Binds and Bundles F-actin to Promote Salmonella Invasion

Myeni

Zhou

2010

Journal of Biological Chemistry

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Salmonella enterica serovar Typhimurium invade non-phagocytic cells by injecting bacterial effector proteins to exploit the host actin cytoskeleton network. SipC is such a Salmonella effector known to nucleate actin, bundle F-actin, and translocate type III effectors. The molecular mechanism of how SipC bundles F-actin and SipC domains responsible for these activities are not well characterized. We successfully separated these activities through a series of genetic deletion/insertions in SipC. We found that the C terminus (amino acids 200 -409) of SipC bundled actin filaments using in vitro biochemical assays. We further demonstrated that amino acid residues 221-260 and 381-409 of full-length SipC were indispensable for its actin binding and bundling activities. Furthermore, Salmonella mutant strains lacking the actin bundling activity were less invasive into HeLa cells. These studies indicate that the C terminus of SipC bundles F-actin to promote Salmonella invasion.

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Salmonella typhimurium leucine‐rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems

Cited by 258 publications

References 63 publications

Functional Transfer of Salmonella Pathogenicity Island 2 to Salmonella bongori and Escherichia coli

Functional Transfer of Salmonella Pathogenicity Island 2 to Salmonella bongori and Escherichia coli

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

The C Terminus of SipC Binds and Bundles F-actin to Promote Salmonella Invasion

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