Growth control in the Salmonella-containing vacuole

Portillo, Francisco García‐del; Núñez-Hernández, Cristina; Eisman, Blanca; Ramos-Vivas, José

doi:10.1016/j.mib.2008.01.001

Cited by 52 publications

(32 citation statements)

References 57 publications

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“…Typhimurium acrA mutant was affected in growth under anaerobic conditions after 24 h [64]. Hence, since the Salmonella -containing vacuole within infected cells is considered hypoxic [65], it can be postulated that inactivation of acrA in the S . Typhi mutant is in fact impairing the ability of the bacteria to replicate under such anaerobic conditions.…”

Section: Discussionmentioning

confidence: 99%

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

2012

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The human-adapted Salmonella enterica serovar Typhi (S. Typhi) causes a systemic infection known as typhoid fever. This disease relies on the ability of the bacterium to survive within macrophages. In order to identify genes involved during interaction with macrophages, a pool of approximately 105 transposon mutants of S. Typhi was subjected to three serial passages of 24 hours through human macrophages. Mutants recovered from infected macrophages (output) were compared to the initial pool (input) and those significantly underrepresented resulted in the identification of 130 genes encoding for cell membrane components, fimbriae, flagella, regulatory processes, pathogenesis, and many genes of unknown function. Defined deletions in 28 genes or gene clusters were created and mutants were evaluated in competitive and individual infection assays for uptake and intracellular survival during interaction with human macrophages. Overall, 26 mutants had defects in the competitive assay and 14 mutants had defects in the individual assay. Twelve mutants had defects in both assays, including acrA, exbDB, flhCD, fliC, gppA, mlc, pgtE, typA, waaQGP, SPI-4, STY1867-68, and STY2346. The complementation of several mutants by expression of plasmid-borne wild-type genes or gene clusters reversed defects, confirming that the phenotypic impairments within macrophages were gene-specific. In this study, 35 novel phenotypes of either uptake or intracellular survival in macrophages were associated with Salmonella genes. Moreover, these results reveal several genes encoding molecular mechanisms not previously known to be involved in systemic infection by human-adapted typhoidal Salmonella that will need to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

2012

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“…The type III secretion system encoded by the Salmonella SPI-2 gene releases effectors that function to both interfere with antimicrobial defense mechanisms of the host and modify Salmonella-containing vacuole to provide optimum living conditions for Salmonella. 22 It was reported that the Salmonella phoPQ system specifically monitors the inner environment of the macrophage and controls the expression of various genes, such as the spvB gene. 23 The SpvB protein has recently been shown to contain an ADP-ribosyltransferase domain in its C-terminus that ADP-ribosylates actin, and this enzymatic activity has been demonstrated to be essential for virulence in mice.…”

Section: S Typhi Plasmid Induces Macrophage Apoptosismentioning

confidence: 99%

A Salmonella enterica serovar Typhi plasmid induces rapid and massive apoptosis in infected macrophages

et al. 2010

Cell Mol Immunol

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pR ST98 is a chimeric plasmid isolated from Salmonella enterica serovar Typhi (S. typhi) that mediates the functions of drug resistance and virulence. Previously, we reported that Salmonella plasmid virulence (spv) genes were present in S. typhi. In our current study, we investigated whether plasmid pR ST98 exhibits significant cytotoxicity in macrophages. pR ST98 was transferred into the avirulent Salmonella enterica serovar Typhimurium (S. typhimurium) strain RIA to create the transconjugant pR ST98 /RIA. The standard S. typhimurium virulent strain SR-11, which carries a 100-kb virulence plasmid, was used as a positive control. The bacterial strains were incubated with a murine macrophage-like cell line (J774A.1) in vitro. Apoptosis of J774A.1 cells was examined by electron microscopy and flow cytometry after annexin-V/propidium iodide labeling, and the survival of Salmonella strains in J774A.1 cells was determined. Results showed that macrophages infected with strain pR ST98 /RIA displayed greater levels of apoptosis than those infected with RIA and that pR ST98 may increase bacterial survival in macrophages. Further studies showed that the pR ST98 -induced death of macrophages was associated with the loss of mitochondrial membrane potential and that pR ST98 may activate caspase-9 and then caspase-3. The research data indicate that the virulence of bacteria that contain the pR ST98 plasmid is enhanced; the presence of this plasmid increases the survival of the bacterial pathogen and acts through the mitochondrial pathway to mediate macrophage apoptosis.

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“…2,10 S. enterica serovar Typhimurium (S. Typhimurium) is an intracellular bacterial pathogen that infects phagocytic and nonphagocytic eukaryotic cells and resides in a specialized phagosomal compartment named the SCV, for Salmonellacontaining vacuole. [11][12][13] In vivo, S. Typhimurium preferentially colonizes macrophages, both in target organs and in lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Salmonella induces aggrephagy of host endomembranes in persistent infections

et al. 2016

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Xenophagy has been studied in epithelial cells infected with Salmonella enterica serovar Typhimurium (S. Typhimurium). Distinct autophagy receptors target this pathogen to degradation after interacting with ubiquitin on the surface of cytosolic bacteria, and the phagophore-and autophagosome-associated protein MAP1LC3/LC3. Glycans exposed in damaged phagosomal membranes and diacylglycerol accumulation in the phagosomal membrane also trigger S. Typhimurium xenophagy. How these responses control intraphagosomal and cytosolic bacteria remains poorly understood. Here, we examined S. Typhimurium interaction with autophagy in fibroblasts, in which the pathogen displays limited growth and does not escape into the cytosol. Live-cell imaging microscopy revealed that S. Typhimurium recruits late endosomal or lysosomal compartments that evolve into a membranous aggregate connected to the phagosome. Active dynamics and integrity of the phagosomal membrane are requisite to induce such aggregates. This membranous structure increases over time to become an aggresome that engages autophagy machinery at late infection times (> 6 h postentry). The newly formed autophagosome harbors LC3 and the autophagy receptor SQSTM1/p62 but is devoid of ubiquitin and the receptor CALCOCO2/NDP52. Live-cell imaging showed that this autophagosome captures and digests within the same vacuole the aggresome and some apposed intraphagosomal bacteria. Other phagosomes move away from the aggresome and avoid destruction. Thus, host endomembrane accumulation resulting from activity of intracellular S. Typhimurium stimulates a novel type of aggrephagy that acts independently of ubiquitin and CALCOCO2, and destroys only a few bacteria. Such selective degradation might allow the pathogen to reduce its progeny and, as a consequence, to establish persistent infections.

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Growth control in the Salmonella-containing vacuole

Cited by 52 publications

References 57 publications

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library

A Salmonella enterica serovar Typhi plasmid induces rapid and massive apoptosis in infected macrophages

Intracellular Salmonella induces aggrephagy of host endomembranes in persistent infections

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