The Icm/Dot type-IV secretion systems of<i>Legionella pneumophila</i>and<i>Coxiella burnetii</i>

Segal, G. M.; Feldman, Michal; Zusman, Tal

doi:10.1016/j.femsre.2004.07.001

Cited by 210 publications

(199 citation statements)

References 119 publications

(272 reference statements)

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“…Despite the fact that Ͼ40 translocated substrates of the Dot/Icm system have been identified, no other substrate is known to play as significant a role in intracellular growth as does SdhA (38). Even so, not all host cells are equally restrictive of the sdhA Ϫ mutant.…”

Section: Discussionmentioning

confidence: 99%

A Legionella pneumophila -translocated substrate that is required for growth within macrophages and protection from host cell death

Laguna

Creasey

et al. 2006

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

200

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Legionella pneumophila requires the Dot/Icm protein translocation system to replicate within host cells as a critical component of Legionnaire's pneumonia. None of the known individual substrates of the translocator have been shown to be essential for intracellular replication. We demonstrate here that mutants lacking the Dot/Icm substrate SdhA were severely impaired for intracellular growth within mouse bone marrow macrophages, with the defect absolute in triple mutants lacking sdhA and its two paralogs. The defect caused by the absence of the sdhA family was less severe during growth within Dictyostelium discoideum amoebae, indicating that the requirement for SdhA shows cell-type specificity. Macrophages harboring the L. pneumophila sdhA mutant showed increased nuclear degradation, mitochondrial disruption, membrane permeability, and caspase activation, indicating a role for SdhA in preventing host cell death. Defective intracellular growth of the sdhA ؊ mutant could be partially suppressed by the action of caspase inhibitors, but caspase-independent cell death pathways eventually aborted replication of the mutant.apoptosis ͉ Dot/Icm ͉ sdhA

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Section: Discussionmentioning

confidence: 99%

A Legionella pneumophila -translocated substrate that is required for growth within macrophages and protection from host cell death

Laguna

Creasey

et al. 2006

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

200

241

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“…To date, type IVB protein substrates have only been identified for the L. pneumophila Icm/Dot secretion system (Segal et al, 2005). Some Icm/Dot substrates possess a Cterminal translocation signal for substrate recognition.…”

Section: The Type Iva Lvh and Type Ivb Icm/dot Secretion Systemsmentioning

confidence: 99%

The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila

2007

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“…Once it has entered the intracellular compartment, B. pseudomallei is able to escape from endocytic vacuoles and move within the cytoplasm and enter neighbouring cells by inducing actin rearrangement, leading to the formation of actin tails and membrane protrusions (Kespichayawattana et al, 2000;Breitbach et al, 2003;Stevens et al, 2005). For many bacterial pathogens, entry and survival within eukaryotic cells is dependent on a functional type III or type IV secretion system (T3SS or T4SS) (Cornelis, 2006;Christie et al, 2005;Segal et al, 2005). The B. pseudomallei genome has the potential to encode three T3SSs (T3SS-1 to T3SS-3) (Attree & Attree, 2001;Rainbow et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages

2007

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In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages The Gram-negative proteobacterium Burkholderia pseudomallei can survive and multiply within a variety of eukaryotic cells, including macrophages. This property is believed to be important for its ability to cause the disease melioidosis in a wide range of animal species, including humans. To identify determinants that are important for the ability of B. pseudomallei to survive within macrophages, in vivo expression technology (IVET) was employed. Several putative macrophage-inducible genes were identified that are likely to contribute to the virulence of B. pseudomallei, including three genes (tssH-5, tssI-5 and tssM-5) located within the same type VI secretion system cluster (tss-5), mntH, encoding a natural resistance-associated macrophage protein (NRAMP)-like manganese ion transporter, and a haem acquisition gene, bhuT. The macrophage-inducibility of the tss-5 gene cluster was confirmed by reporter gene analysis. Construction of tssH-5 and bhuT null mutants indicated that expression of the tss-5 unit and the bhu operon were not required for intramacrophage survival. A further five tss units were identified within the B. pseudomallei genome that, together with tss-5, account for approximately 2.3 % of the total genome size. The presence of six type VI secretion systems in this organism is likely to be an important factor in making this bacterium such a versatile pathogen. INTRODUCTIONMelioidosis is the name given to any infection caused by Burkholderia pseudomallei, a saprophytic, Gram-negative bacillus found in wet soil and pooled water, particularly in south-east Asia and northern Australia (White, 2003). It is principally acquired following inoculation of lesions in the skin by contaminated soil and water, with the highest incidence of the disease occurring during the rainy and monsoon seasons (Dance, 1991;White, 2003). Another important route of infection is inhalation of contaminated particles. The clinical spectrum of melioidosis ranges from an acute fulminant septicaemia to chronic localized infections, often affecting the lung, and is usually characterized by abscess formation. No vaccines are available, and antibiotic therapy is problematic due to the intrinsic high resistance of B. pseudomallei to many antibiotics. The overall mortality of melioidosis patients is 50 % (White, 2003).Certain features of melioidosis suggest that B. pseudomallei is a facultative intracellular pathogen. These include the occurrence of long periods of latency (a recent case report suggests this can be as long as 62 years), relapses due to recrudescence of a persistent primary infection, and the activation of a cellular immune response during melioidosis (Chaowagul et al., 1993;Ngauy et al., 2005). Consistent with this, B. pseudomallei has been shown to survive and multiply within non-phagocytic cells, macrophages and free-living amoebae (Pruksachartvuthi et al., 1990;Jones et a...

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The Icm/Dot type-IV secretion systems ofLegionella pneumophilaandCoxiella burnetii

Cited by 210 publications

References 119 publications

A Legionella pneumophila -translocated substrate that is required for growth within macrophages and protection from host cell death

A Legionella pneumophila -translocated substrate that is required for growth within macrophages and protection from host cell death

The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila

In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages

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