Early Events in Phagosome Establishment Are Required for Intracellular Survival of Legionella pneumophila

Wiater, Lawrence A.; Dunn, Kenneth W.; Maxfield, Frederick R.; Shuman, Howard A.

doi:10.1128/.66.9.4450-4460.1998

Cited by 19 publications

(21 citation statements)

References 33 publications

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“…Thus, while intracellular replication of L. longbeachaea is totally independent of the growth phase, bacterial motility is triggered by L. longbeachaea only at the postexponential phase, suggesting a divergence in global regulatory networks of virulence-related phenotypes in both species. Examination of trafficking of L. pneumophila in human macrophages has shown that this bacterium resides in a phagosome that does not interact with the endocytic pathway (Horwitz, 1983a;Roy et al, 1998;Vogel et al, 1998;Wiater et al, 1998). The L. pneumophila phagosome excludes both early and late endosomal markers such as Rab5, LAMP-1, LAMP-2 and Cathepsin D (Horwitz and Silverstein, 1981;Sturgill-Koszycki and Swanson, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Legionella pneumophila replicates in alveolar macrophages, which is necessary for the manifestation of legionnaires' disease (Davis et al, 1983). After phagocytosis by quiescent macrophages, L. pneumophila is localized in a unique phagosome that is isolated from the endocytic pathway (Horwitz, 1983a;Roy et al, 1998;Vogel et al, 1998;Wiater et al, 1998). The Legionella-containing phagosome (LCP) excludes endocytic markers, including the lysosomal associated membrane glycoproteins, LAMP-1 and LAMP-2, as well as the lysosomal acid protease Cathepsin D (Clemens and Horwitz, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome

Asare¹,

Kwaik²

2007

Cell Microbiol

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SummaryLegionella pneumophila is the predominant cause of Legionnaires' disease in the USA and Europe in contrast to Legionella longbeachaea, which is the leading cause of the disease in Western Australia. The ability of L. pneumophila to replicate intracellularly is triggered at the post-exponential phase along with expression of other virulence traits, such as motility. We show that while motility of L. longbeachaea is triggered upon growth transition into postexponential phase, its ability to proliferate intracellularly is totally independent of the bacterial growth phase. Within macrophages, L. pneumophila replicates in a phagosome that excludes early and late endocytic markers and is surrounded by the rough endoplasmic reticulum (RER). In contrast, the L. longbeachaea phagosome colocalizes with the early endosomal marker early endosomal antigen 1 (EEA1) and the late endosomal markers lysosomal associated membrane glycoprotein 2 (LAMP-2) and mannose 6-phosphate receptor (M6PR), and is surrounded by the RER. The L. longbeachaea phagosome does not colocalize with the vacuolar ATPase (vATPase) proton pump, and the lysosomal luminal protease Cathepsin D, or the lysosomal tracer Texas red Ovalbumin (TROV). Intracellular proliferation of L. longbeachaea occurs in LAMP-2-positive phagosomes that are remodelled by the RER. Despite their distinct trafficking, both L. longbeachaea and L. pneumophila can replicate in communal phagosomes whose biogenesis is predominantly modulated by L. longbeachaea into LAMP-2-positive phagosomes. In addition, the L. pneumophila dotA mutant is rescued for intracellular replication if it co-inhabits the phagosome with L. longbeachaea. During late stages of infection, L. longbeachaea escape into the cytoplasm, prior to lysis of the macrophage, similar to L. pneumophila. We conclude that the L. longbeachaea phagosome matures to a non-acidified late endosome-like stage that is remodelled by the RER, indicating an idiosyncratic trafficking of L. longbeachaea compared with other intracellular pathogens, and a divergence in its intracellular lifestyle from L. pneumophila. In addition, re-routing biogenesis of the L. pneumophila phagosome into a late endosome controlled by L. longbeachaea has no effect on intracellular replication.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome

Asare¹,

Kwaik²

2007

Cell Microbiol

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“…Results obtained with D. discoideum are of general interest because the infection processes of macrophages and D. discoideum with L. pneumophila appear very similar Lu and Clarke, 2005). For example, in macrophages and in D. discoideum the endolysosomal pathway is avoided and fusion of the phagosome with lysosomes is inhibited early in infection (Roy et al ., 1998;Wiater et al ., 1998;. In both hosts the phagosome is surrounded by ribosomes after a few hours and Legionella dot/icm mutants cannot proliferate (Horwitz, 1983;.…”

Section: Introductionmentioning

confidence: 99%

Dictyostelium transcriptional host cell response upon infection with Legionella

et al. 2006

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SummaryDifferential gene expression of Dictyostelium discoideum after infection with Legionella pneumophila was investigated using DNA microarrays. Investigation of a 48 h time course of infection revealed several clusters of co-regulated genes, an enrichment of preferentially up-or downregulated genes in distinct functional categories and also showed that most of the transcriptional changes occurred 24 h after infection. A detailed analysis of the 24 h time point post infection was performed in comparison to three controls, uninfected cells and co-incubation with Legionella hackeliae and L. pneumophila ∆ ∆ ∆ ∆ dotA . One hundred and thirty-one differentially expressed D. discoideum genes were identified as common to all three experiments and are thought to be involved in the pathogenic response. Functional annotation of the differentially regulated genes revealed that apart from triggering a stress response Legionella apparently not only interferes with intracellular vesicle fusion and destination but also profoundly influences and exploits the metabolism of its host. For some of the identified genes, e.g. rtoA involvement in the host response has been demonstrated in a recent study, for others such a role appears plausible. The results provide the basis for a better understanding of the complex host-pathogen interactions and for further studies on the Dictyostelium response to Legionella infection.

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“…Establishment and maintenance of LCV membrane integrity are essential for protection of L. pneumophila from innate immune cytosolic sensing (Creasey & Isberg, 2014;Liu et al, 2018). The inability of a bacterial mutant to properly form the LCV or maintain its integrity results in a severe intracellular growth defect and pathogen clearance (Creasey & Isberg, 2012;Wiater, Dunn, Maxfield, & Shuman, 1998).…”

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confidence: 99%

Components of the endocytic and recycling trafficking pathways interfere with the integrity of the Legionella ‐containing vacuole

Anand

Choi

Isberg

2020

Cellular Microbiology

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Legionella pneumophila requires the Dot/Icm translocation system to replicate in a vacuolar compartment within host cells. Strains lacking the translocated substrate SdhA form a permeable vacuole during residence in the host cell, exposing bacteria to the host cytoplasm. In primary macrophages, mutants are defective for intracellular growth, with a pyroptotic cell death response mounted due to bacterial exposure to the cytosol. To understand how SdhA maintains vacuole integrity during intracellular growth, we performed high‐throughput RNAi screens against host membrane trafficking genes to identify factors that antagonise vacuole integrity in the absence of SdhA. Depletion of host proteins involved in endocytic uptake and recycling resulted in enhanced intracellular growth and lower levels of permeable vacuoles surrounding the ΔsdhA mutant. Of interest were three different Rab GTPases involved in these processes: Rab11b, Rab8b and Rab5 isoforms, that when depleted resulted in enhanced vacuole integrity surrounding the sdhA mutant. Proteins regulated by these Rabs are responsible for interfering with proper vacuole membrane maintenance, as depletion of the downstream effectors EEA1, Rab11FIP1, or VAMP3 rescued vacuole integrity and intracellular growth of the sdhA mutant. To test the model that specific vesicular components associated with these effectors could act to destabilise the replication vacuole, EEA1 and Rab11FIP1 showed increased density about the sdhA mutant vacuole compared with the wild type (WT) vacuole. Depletion of Rab5 isoforms or Rab11b reduced this aberrant redistribution. These findings are consistent with SdhA interfering with both endocytic and recycling membrane trafficking events that act to destabilise vacuole integrity during infection.

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Early Events in Phagosome Establishment Are Required for Intracellular Survival of Legionella pneumophila

Cited by 19 publications

References 33 publications

Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome

Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome

Dictyostelium transcriptional host cell response upon infection with Legionella

Components of the endocytic and recycling trafficking pathways interfere with the integrity of the Legionella ‐containing vacuole

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