A role for the <i>Salmonella</i> Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

Chong, Audrey; Starr, Tregei; Finn, Ciaran E.; Steele‐Mortimer, Olivia

doi:10.1111/mmi.14361

Cited by 28 publications

(32 citation statements)

References 57 publications

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“…Previous work has demonstrated important role(s) for SipA in shaping the S.Tm niche in the vacuole or cytosol after host cell entry [45,[52][53][54]. Our data do not refute that SipA can act in this fashion also in the intact epithelium of adult mice.…”

Section: Plos Pathogenscontrasting

confidence: 88%

“…Several TTSS-1 effectors, and in particular SipA, have been shown to shape the intracellular S. Tm niche and/or promote the bacterium's replicative potential subsequent to host cell entry [45,[52][53][54]. This could potentially skew the results above that rely on the pssaG-GFP reporter to quantify invasion efficiency in vivo.…”

Section: Experiments In Inflammasome-deficient Mice Verify the Importmentioning

confidence: 99%

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Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium

et al. 2020

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Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial cell invasion. According to this model, the Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia-and filopodia-containing ruffles and cooperative S.Tm uptake. However, cell line experiments poorly recapitulate many of the cell and tissue features encountered in the host's gut mucosa. Here, we employed bacterial genetics and multiple imaging modalities to compare S.Tm invasion of cultured epithelial cell lines and the gut absorptive epithelium in vivo in mice. In contrast to the prevailing rufflemodel, we find that absorptive epithelial cell entry in the mouse gut occurs through "discreetinvasion". This distinct entry mode requires the conserved TTSS-1 effector SipA, involves modest elongation of local microvilli in the absence of expansive ruffles, and does not favor cooperative invasion. Discreet-invasion preferentially targets apicolateral hot spots at cellcell junctions and shows strong dependence on local cell neighborhood. This proof-of-principle evidence challenges the current model for how S.Tm can enter gut absorptive epithelial cells in their intact in vivo context.

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Section: Plos Pathogenscontrasting

confidence: 88%

Section: Experiments In Inflammasome-deficient Mice Verify the Importmentioning

confidence: 99%

Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium

et al. 2020

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“…A reporter system for quantitative analyses of intracellular subpopulation was established using a promoter responsive to host cell cytosolic glucose‐6‐phosphate (G6P) to drive fluorescent protein expression. The G6P reporter was introduced by Schmutz et al (Schmutz et al, ) and subsequently applied in several studies (Chong, Starr, Finn, & Steele‐Mortimer, ; Cooper, Chong, Starr, Finn, & Steele‐Mortimer, ; Lau et al, ; Spinnenhirn et al, ). Here, we demonstrate that SCV rupture and cytosolic release of Salmonella in the early intracellular phase are functions of the experimental settings in cell culture models and linked to the presence of SPI1‐T3SS effector protein SopE.…”

Section: Introductionmentioning

confidence: 99%

Presence of SopE and mode of infection result in increasedSalmonella‐containing vacuole damage and cytosolic release during host cell infection bySalmonella enterica

Röder

Hensel

2020

Cellular Microbiology

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Salmonella enterica serovar Typhimurium (STM) is an invasive, facultative intracellular pathogen that has evolved sophisticated molecular mechanisms to establish an intracellular niche within a specialised vesicular compartment, the Salmonella‐containing vacuole (SCV). The loss of the SCV and release of STM into the cytosol of infected host cells was observed, and a bimodal intracellular lifestyle of STM in the SCV versus life in the cytosol is currently discussed. We set out to investigate the parameters affecting SCV integrity and cytosolic release. A fluorescent protein‐based cytosolic reporter approach was established to quantify, time‐resolved, and on a single cell level, the release of STM into the cytosol of host cells. We observed that the extent of SCV damage and cytosolic release is highly dependent on experimental conditions such as multiplicity of infection, type of host cell line, and STM strain background. Trigger invasion mediated by the Salmonella Pathogenicity Island 1‐encoded type III secretion system (SPI1‐T3SS) and its effector proteins promoted cytosolic release, whereas cytosolic bacteria were rarely observed if entry was mediated by zipper invasion. Presence of SPI1‐T3SS effector SopE was identified as major factor for damage of the SCV in the early phase after STM invasion and sopE‐expressing strains showed higher levels of cytosolic release.

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“…Therefore, we used single-cell analysis by fluorescent microscopy to evaluate if ER1175 and ER278, carrying different hilD alleles, differ in their ability to replicate within human or swine cells. As it was reported that cells containing more than 50 bacteria can be indicative of the hyper-replicating phenotype 36 , we calculated the statistical differences in occurrence of cells containing ≥ 50 bacteria between the two strains. The majority of human and swine cells infected by ER1175 carried more than 50 bacteria (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mutation of hilD in a Salmonella Derby lineage linked to swine adaptation and reduced risk to human health

Tambassi

Berni

Bracchi

et al. 2020

Sci Rep

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Salmonella enterica variants exhibit diverse host adaptation, outcome of infection, and associated risk to food safety. Analysis of the distribution of Salmonella enterica serovar Derby (S. Derby) subtypes in human and swine identified isolates with a distinct PFGE profile that were significantly under-represented in human infections, consistent with further host adaptation to swine. Here we show that isolates with this PFGE profile form a distinct phylogenetic sub-clade within S. Derby and exhibit a profound reduction in invasion of human epithelial cells, and a relatively small reduction in swine epithelial cells. A single missense mutation in hilD, that encodes the master-regulator of the Salmonella Pathogenicity Island 1 (SPI-1), was present in the adapted lineage. The missense mutation resulted in a loss of function of HilD that accounted for reduced invasion in human epithelial cells. The relatively small impact of the mutation on interaction with swine cells was consistent with an alternative mechanism of invasion in this pathogen-host combination.

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A role for the Salmonella Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

Cited by 28 publications

References 57 publications

Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium

Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium

Presence of SopE and mode of infection result in increasedSalmonella‐containing vacuole damage and cytosolic release during host cell infection bySalmonella enterica

Mutation of hilD in a Salmonella Derby lineage linked to swine adaptation and reduced risk to human health

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