pathogenicity islands encoding type III secretion systems

Hansen-Wester, Imke; Hensel, Michael

doi:10.1016/s1286-4579(01)01411-3

Cited by 333 publications

(269 citation statements)

References 66 publications

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“…3a), because T3SS2 belongs to the Inv-Mxi-Spa secretion system that can translocate effector proteins into host cells and induce actin rearrangement leading to bacterial internalization (Handa et al, 2007;Hansen-Wester & Hensel, 2001;Jepson et al, 2003;Pizarro-Cerda & Cossart, 2006;Schlumberger & Hardt, 2006). A possible reason for this discrepancy is that the strain used in our study lacks the T3SS2 substrates responsible for efficient invasion; our results showed that invasiveness of NY-4 is less than that of other strains of V. parahaemolyticus (e.g.…”

Section: Discussionmentioning

confidence: 73%

Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines

2009

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The Vibrio parahaemolyticus type III secretion system 1 (T3SS1) induces cytotoxicity in mammalian epithelial cells. We characterized the cell death phenotype in both epithelial (HeLa) and monocytic (U937) cell lines following infection with V. parahaemolyticus. Using a combination of the wild-type strain and gene knockouts, we confirmed that V. parahaemolyticus strain NY-4 was able to induce cell death in both cell lines via a T3SS1-dependent mechanism. Bacterial contact, but not internalization, was required for T3SS1-induced cytotoxicity. The mechanism of cell death involves formation of a pore structure on the surface of infected HeLa and U937 cells, as demonstrated by cellular swelling, uptake of cell membrane-impermeable dye and protection of cytotoxicity by osmoprotectant (PEG3350). Western blot analysis showed that poly ADP ribose polymerase (PARP) was not cleaved and remained in its full-length active form. This result was evident for seven different V. parahaemolyticus strains. V. parahaemolyticus-induced cytotoxicity was not inhibited by addition of the pan-caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) or the caspase-1 inhibitor N-acetyl-tyrosyl-valylalanyl-aspartyl-aldehyde (Ac-YVAD-CHO); thus, caspases were not involved in T3SS1-induced cytotoxicity. DNA fragmentation was not evident following infection and autophagic vacuoles were not observed after monodansylcadaverine staining. We conclude that T3SS1 of V. parahaemolyticus strain NY-4 induces a host cell death primarily via oncosis rather than apoptosis, pyroptosis or autophagy. INTRODUCTIONVibrio parahaemolyticus is a Gram-negative food-borne pathogen that is commonly associated with consumption of raw or undercooked seafood (Joseph et al., 1982). Symptoms of infection include diarrhoea, nausea, vomiting, headache, fever and chills. In addition to typical gastrointestinal infections, approximately 5 % of V. parahaemolyticus infections advance to septicaemia (Hlady & Klontz, 1996) and these infections may be fatal, especially in immunocompromised patients or those with a preexisting medical condition such as liver disease or diabetes (Yeung & Boor, 2004).Thermostable direct haemolysin (TDH) is considered the primary virulence factor in V. parahaemolyticus. In addition to its ability to form pores in red blood cells, TDH causes increased short circuit current, increased Cl 2 secretion in human colonic epithelial cells, and enhanced Ca 2+ entry from the extracellular medium (Takahashi et al., 2001). An early study of a tdh deletion mutant demonstrated significantly reduced ability to cause fluid accumulation in ileal loops of a rabbit model (Nishibuchi et al., 1992). In contrast, Park et al. (2004) showed that a tdh deletion mutant has the ability to cause fluid accumulation in the ligated intestine of rabbits. Furthermore, both TDH-positive and -negative strains of V. parahaemolyticus can disrupt the epithelial tight junction, a precursor to dissemination of bacteria into the circulation (Lynch et a...

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Section: Discussionmentioning

confidence: 73%

Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines

2009

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“…T he species Salmonella enterica is a classic example of the facultative intracellular pathogen that can cause acute and persistent infections (1)(2)(3)(4). Typhoid fever is a serious manifestation of systemic salmonellosis in humans and involves an estimated 16.6 million new cases per year (2) with between 2% and 5% of the cases developing into the carrier state (3,4).…”

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confidence: 99%

“…Much of the knowledge of salmonellosis pathogenesis comes from work on the murine salmonellosis model (1,5), and this model has been used to define bacterial virulence factors (1,6,7). An important virulence trait of Salmonella is its ability to invade and grow within host cells, and many of the genetic determinants essential for these processes have been well characterized (8)(9)(10)(11).…”

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confidence: 99%

Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica

Clements

Eriksson

Thompson

et al. 2002

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

154

133

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For many pathogens, the ability to regulate their replication in host cells is a key element in establishing persistency. Here, we identified a single point mutation in the gene for polynucleotide phosphorylase (PNPase) as a factor affecting bacterial invasion and intracellular replication, and which determines the alternation between acute or persistent infection in a mouse model for Salmonella enterica infection. In parallel, with microarray analysis, PNPase was found to affect the mRNA levels of a subset of virulence genes, in particular those contained in Salmonella pathogenicity islands 1 and 2. The results demonstrate a connection between PNPase and Salmonella virulence and show that alterations in PNPase activity could represent a strategy for the establishment of persistency.T he species Salmonella enterica is a classic example of the facultative intracellular pathogen that can cause acute and persistent infections (1-4). Typhoid fever is a serious manifestation of systemic salmonellosis in humans and involves an estimated 16.6 million new cases per year (2) with between 2% and 5% of the cases developing into the carrier state (3, 4).Much of the knowledge of salmonellosis pathogenesis comes from work on the murine salmonellosis model (1, 5), and this model has been used to define bacterial virulence factors (1, 6, 7). An important virulence trait of Salmonella is its ability to invade and grow within host cells, and many of the genetic determinants essential for these processes have been well characterized (8-11). Invasion of epithelial cells requires the expression of a type III secretion apparatus, which translocates effector proteins from the bacterium to the host cell, inducing the cell to internalize the bacteria by bacterial-mediated endocytosis (8,11). Proteins involved in this process are encoded by a large cluster of genes collectively termed Salmonella pathogenicity island 1 (SPI 1). The ability to grow intracellularly, once internalized within the host cell, requires the coordinate expression of additional sets of virulence factors (6), such as SPI 2 (1, 10).Although chronic carriage of Salmonella is recognized as a significant complication that facilitates spread of the disease (2) and predisposes victims to additional clinical conditions (12, 13) the mechanism underlying persistency has remained poorly understood. We discovered the link between polynucleotide phosphorylase (PNPase) and chronic infection while characterizing a mutant of Salmonella typhimurium that was defective in its expression of virulence-associated AgfA fimbriae and known to establish persistent infection in BALB͞c mice (14). Materials and Methods Mapping and Sequencing of MC2 Mutation.A random Tn10camd insertion library from S. typhimurium 14028 (22) was transduced into MC1 by P22 transduction selecting for chloramphenicolresistant colonies. Transductants were pooled and used to propagate phage KB1, which was then used to transduce MC2. Chloramphenicol-resistant colonies were screened for agf expression on Congo red pla...

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“…S. enterica is also a facultative intracellular pathogen that can survive phagocytosis by macrophages and replicate inside eukaryotic host cells. These two hallmarks of pathogenesis are linked to the presence of two pathogenicity islands (reviewed in reference 14). Salmonella pathogenicity island 1 (SPI1) encodes a type III secretion system (T3SS) that has a function for bacterial invasion (11) and further interactions between Salmonella and enterocytes (45).…”

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confidence: 99%

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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pathogenicity islands encoding type III secretion systems

Cited by 333 publications

References 66 publications

Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines

Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines

Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica

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

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