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EcoSal Plus

Domain 8:

Pathogenesis

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  • Authors: Jason Szeto1, and John H. Brumell2,3
  • Editor: Michael S. Donnenberg4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Infection, Immunity, Injury, and Repair Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8; 2: Infection, Immunity, Injury, and Repair Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8; 3: Department of Medical Genetics and Microbiology, University of Toronto, #4388, Medical Sciences Building, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada M5S 1A8; 4: University of Maryland, School of Medicine, Baltimore, MD
  • Received 02 December 2004 Accepted 18 February 2005 Published 25 July 2005
  • Address correspondence to John H. Brumell john.brumell@sickkids.ca
image of <span class="jp-bold">Intracellular Voyeurism: Examining the Modulation of Host Cell Activities by</span>
<span class="jp-italic">Salmonella enterica Serovar Typhimurium</span>
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  • Abstract:

    spp. can infect host cells by gaining entry through phagocytosis or by inducing host cell membrane ruffling that facilitates bacterial uptake. With its wide host range, serovar Typhimurium has proven to be an important model organism for studying intracellular bacterial pathogenesis. Upon entry into host cells, serovar Typhimurium typically resides within a membrane-bound compartment termed the -containing vacuole (SCV). From the SCV, serovar Typhimurium can inject several effector proteins that subvert many normal host cell systems, including endocytic trafficking, cytoskeletal rearrangements, lipid signaling and distribution, and innate and adaptive host defenses. The study of these intracellular events has been made possible through the use of various imaging techniques, ranging from classic methods of transmission electron microscopy to advanced livecell fluorescence confocal microscopy. In addition, DNA microarrays have now been used to provide a "snapshot" of global gene expression in serovar Typhimurium residing within the infected host cell. This review describes key aspects of -induced subversion of host cell activities, providing examples of imaging that have been used to elucidate these events. Serovar Typhimurium engages specific host cell machinery from initial contact with the host cell to replication within the SCV. This continuous interaction with the host cell has likely contributed to the extensive arsenal that serovar Typhimurium now possesses, including two type III secretion systems, a range of ammunition in the form of TTSS effectors, and a complex genetic regulatory network that coordinates the expression of hundreds of virulence factors.

  • Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2

Key Concept Ranking

Bacterial Proteins
0.5335822
Bacterial Pathogenesis
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Major Histocompatibility Complex Class I
0.4267827
0.5335822

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ecosalplus.2.2.2.citations
ecosalplus/1/2
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/content/journal/ecosalplus/10.1128/ecosalplus.2.2.2
2005-07-25
2017-04-27

Abstract:

spp. can infect host cells by gaining entry through phagocytosis or by inducing host cell membrane ruffling that facilitates bacterial uptake. With its wide host range, serovar Typhimurium has proven to be an important model organism for studying intracellular bacterial pathogenesis. Upon entry into host cells, serovar Typhimurium typically resides within a membrane-bound compartment termed the -containing vacuole (SCV). From the SCV, serovar Typhimurium can inject several effector proteins that subvert many normal host cell systems, including endocytic trafficking, cytoskeletal rearrangements, lipid signaling and distribution, and innate and adaptive host defenses. The study of these intracellular events has been made possible through the use of various imaging techniques, ranging from classic methods of transmission electron microscopy to advanced livecell fluorescence confocal microscopy. In addition, DNA microarrays have now been used to provide a "snapshot" of global gene expression in serovar Typhimurium residing within the infected host cell. This review describes key aspects of -induced subversion of host cell activities, providing examples of imaging that have been used to elucidate these events. Serovar Typhimurium engages specific host cell machinery from initial contact with the host cell to replication within the SCV. This continuous interaction with the host cell has likely contributed to the extensive arsenal that serovar Typhimurium now possesses, including two type III secretion systems, a range of ammunition in the form of TTSS effectors, and a complex genetic regulatory network that coordinates the expression of hundreds of virulence factors.

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Figures

Image of Figure 1
Figure 1

Note the wider base of the complex, involved in association with the bacterial cell wall, and the needlelike projection composed of PrgI protein through which effectors are translocated. Bar = 30 nm.

Reproduced from Marlovits et al. (2004), 1040--1042, with permission. Copyright (2004) AAAS.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 2
Figure 2

Arrow indicates serovar Typhimurium in nascent -containing vacuoles (SCV) after entry into the host cell.

Image courtesy of B. Brett Finlay, University of British Columbia.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 3

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 4

Image courtesy of B. Brett Finlay, University of British Columbia.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 5

HeLa cells expressing Rab7-GFP were infected with serovar Typhimurium, and the kinetics of Rab7 recruitment to the SCV was measured by using FRAP. Rectangle and circle indicate the positions of SCV and late-endocytic structures, respectively, that were selected for photobleaching. Note that Rab7-GFP fluorescence recovery is similar between both regions subjected to photobleaching, indicating active Rab7-GFP cycling on the SCV. Bar = 10 μm.

Reproduced from Marsman et al. (2004), 2954--2964 (published online before print as 10.1091/mbc.E03-08-0614), with permission of the American Society for Cell Biology.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 6
Figure 6

(A) Henle cells infected with wild-type serovar Typhimurium exhibit long filamentous LAMP-1 structures (green) emanating from the bacteria (red). (B) Cells infected with a serovar Typhimurium SPI-2 mutant do not exhibit the Sif phenotype.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 7
Figure 7

HeLa cells were infected with serovar Typhimurium, fixed 6 h after infection, and costained for LAMP-2 (A; green) and cathepsin D (B; red). Note cathepsin D localizing along Sif structures indicated by LAMP-2 staining. Arrowheads indicate intracellular bacteria residing in SCVs.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 8
Figure 8

HeLa cells were transfected with a vector encoding SifA-GFP. After 16 to 20 h, cells were fixed, immunostained for LAMP-1 (A; red), and analyzed by confocal microscopy. While predominantly cytosolic, the SifA-GFP (B; green) also localizes to filamentous LAMP-1 structures.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 9

(Left) RAW 264.7 cells were fixed 2 h after infection by invasive serovar Typhimurium and stained for LAMP-1 (red) and bacteria (blue). (Right) Ubiquitinated proteins stained with monoclonal antibody (FK2) that recognizes mono- and polyubiquitinated proteins, but not free ubiquitin. Arrow indicates cytosolic bacteria. Arrowhead indicates bacteria residing in LAMP-1 SCV. Bar = 5 μm.

Reproduced from Perrin et al. (2004), 806--811, with permission from Elsevier.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 10

HeLa cells were infected with wild-type serovar Typhimurium (A) or an isogenic mutant bearing a disruption in the gene (B). Both strains carried a plasmid expressing SifA with two internal HA epitope tags. Infected cells were fixed 8 h after infection, coimmunostained for LAMP-2 and HA epitope, and analyzed by confocal microscopy. HA-tagged SifA protein was localized predominantly on Sifs in wild-type infected cells (A, arrows). In cells infected with the mutant, SifA was also localized to filamentous structures exhibiting punctate rather than continuous distribution of LAMP-2 (B, arrows), representing a phenotype known as “pseudo-Sifs.” (C) Cells were infected as described in panels A and B, and the number of Sifs (filled boxes) and pseudo-Sifs (open boxes) formed was determined. Bar = 10 μm.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 11

HeLa cells were infected with wild-type serovar Typhimurium for 18 h, fixed and stained for tubulin (red) and LAMP-1 (green). Yellow indicates colocalization of LAMP-1 filamentous structures (Sifs) with the microtubule network.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 12

Cells were infected with wild-type serovar Typhimurium (green) for 10 h. Red signal in merged images shows distribution of kinesin or dynein, as indicated. Host cell perimeters are outlined by dotted line.

Reproduced from Guo et al. (1997), 250--253, with permission of the publisher.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 13
Figure 13

HeLa cells were transfected with Rab7-GFP (A, C; green) or with RILP-GFP (D, F; green) 2 h after infection by serovar Typhimurium. Cells were incubated another 12 to 16 h, fixed, and stained for LAMP-1. Arrows point to Sifs, identified as filamentous, LAMP-positive structures. Solid arrows correspond to the magnified inset in each panel. Note that Rab7-GFP is localized to Sifs (A, C) but that RILP-GFP is not (D, F).

Reproduced from Harrison et al. (2004), 3146–3154 (published online before print as 10.1091/mbc.E04-02-0092), with permission of the American Society for Cell Biology.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 14
Figure 14

Peritoneal macrophages from periodate-elicited C57BL/6 mice were infected with wild-type (A) or SPI-2 mutant (B) serovar Typhimurium. NADPH oxidase activity was detected as cerium perhydroxide precipitate. Note the dark precipitate localized on the SCV surrounding SPI-2 mutant (B) but not wild-type serovar Typhimurium (A).

Reproduced from Vazquez-Torres et al. (2000), 1655–1658, with permission of the publisher.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Image of Figure 15
Figure 15

RAW 264.7 macrophages were infected with wild-type serovar Typhimurium (A) or were left uninfected (B). Cells were processed for transmission electron microscopy 2 h after infection. Note the aggregation of chromatin and vacuolization of the cytosol, which is indicative of apoptotic cell death, in the macrophage infected with wild-type serovar Typhimurium (A).

Reproduced from Monack et al. (1996), 9833–9838. Copyright (1996) National Academy of Sciences.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Figure 16

COS-2 cells transfected with SipB-GFP were fixed and subjected to immunoelectron microscopy with rabbit anti-GFP antisera and gold-labeled anti-rabbit secondary antibody. (A) SipB-GFP localized to multimembrane-layered structures near mitochondria. (B and C) Mitochondria (B and C, right side) appeared to be fusing with SifB-containing multilamellar structures (B and C, left side). Arrows and box indicate regions where apparent membrane fusion is occurring. (D) Mitochondria surrounded by SipB-induced multilamellar structure. Bars = 250 nm.

Reproduced from Hernandez et al. (2003), 1123–1131, with permission of The Rockefeller University Press.

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2
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Tables

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Table 1

Proteins secreted by serovar Typhimurium type III secretion systems

Citation: Szeto J, Brumell J. 2005. , EcoSal Plus 2005; doi:10.1128/ecosalplus.2.2.2

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