Salmonella SipA mimics a cognate SNARE for host Syntaxin8 to promote fusion with early endosomes

Singh, Pawan; Kapoor, Anjali; Lomash, Richa Madan; Kumar, Kamal; Kamerkar, Sukrut C.; Pucadyil, Thomas J.; Mukhopadhyay, Asok

doi:10.1083/jcb.201802155

Cited by 28 publications

(33 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It displaces host actin‐binding proteins from F‐actin and prevents actin severing, thus contributing to the actin cytoskeleton rearrangements that are required for Salmonella invasion (Zhou et al , ; McGhie et al , ; Higashide et al , ; Lilic et al , ; McGhie et al , ; Lhocine et al , ). Other activities that have been attributed to SipA include Caspase‐3 cleavage and activation (Cain et al , ; McIntosh et al , ), induction of CXC chemokine expression through phosphorylation of IL‐8‐transcription regulatory proteins, JUN and p38MAK (Figueiredo et al , ) and promoting fusion with early endosomes (Singh et al , ). Of relevance to this study, several groups have shown that SipA is also involved in intracellular replication, with the consensus being that it promotes vacuolar replication (Brawn et al , ; Klein et al , ; Singh et al , ; Zhang et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Other activities that have been attributed to SipA include Caspase-3 cleavage and activation (Cain et al, 2008;McIntosh et al, 2017), induction of CXC chemokine expression through phosphorylation of IL-8-transcription regulatory proteins, JUN and p38MAK (Figueiredo et al, 2009) and promoting fusion with early endosomes (Singh et al, 2018). Of relevance to this study, several groups have shown that SipA is also involved in intracellular replication, with the consensus being that it promotes vacuolar replication (Brawn et al, 2007;Klein et al, 2017;Singh et al, 2018;Zhang et al, 2018). Here, we found that SipA has no effect on replication per se.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Chong

Starr

Finn

et al. 2019

Molecular Microbiology

View full text Add to dashboard Cite

Summary Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that invades the intestinal epithelium. Following invasion of epithelial cells, Salmonella survives and replicates within two distinct intracellular niches. While all of the bacteria are initially taken up into a membrane bound vacuole, the Salmonella‐containing vacuole or SCV, a significant proportion of them promptly escape into the cytosol. Cytosolic Salmonella replicates more rapidly compared to the vacuolar population, although the reasons for this are not well understood. SipA, a multi‐function effector protein, has been shown to affect intracellular replication and is secreted by cytosolic Salmonella via the invasion‐associated Type III Secretion System 1 (T3SS1). Here, we have used a multipronged microscopy approach to show that SipA does not affect bacterial replication rates per se, but rather mediates intra‐cytosolic survival and/or initiation of replication following bacterial egress from the SCV. Altogether, our findings reveal an important role for SipA in the early survival of cytosolic Salmonella.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Chong

Starr

Finn

et al. 2019

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…VAMP7 is the v-SNARE in the SNARE complex for heterotypic LE/lysosome fusions with the t-SNAREs STX7, STX8, and VTI1B [70, 71] being replaced by VAMP8 in homotypic LE fusions [72, 73]. In fact, the presence of VTI1B and STX8 on early SCV [69, 74] and their role in STM replication [54], as well as the involvement of VAMP8 in STM invasion were already shown [75]. However, their interaction with SIF remains unclear, except VAMP8 silencing causing SIF reduction identified here (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

“…Alternatively, this might happen via SPI2-T3SS effector PipB2 that was identified in the recent BioID screen as interactor of VAMP2 [104]. Furthermore, in homotypic EE fusion STX16 is replaced by STX13 [122], and STX13 was previously shown to be present on early SCV [74, 123]. While the exact role of RAB3A and the identity of SNAREs involved remain to be determined, this might indicate that the interception of secretory vesicles depends on a SNARE complex comprising a distinct combination of the abovementioned SNAREs as represented in Figure 8ii.…”

Section: Discussionmentioning

confidence: 99%

A trafficome-wide RNAi screen reveals deployment of early and late secretory host proteins and the entire late endo-/lysosomal vesicle fusion machinery by intracellularSalmonella

Kehl

Göser

Reuter

et al. 2019

Preprint

View full text Add to dashboard Cite

38 The intracellular lifestyle of Salmonella enterica is characterized by the formation of a 39 replication-permissive membrane-bound niche, the Salmonella-containing vacuole (SCV). A 40 further consequence of the massive remodeling of the host cell endosomal system, intracellular 41 Salmonella establish a unique network of various Salmonella-induced tubules (SIT). The 42 bacterial repertoire of effector proteins required for the establishment for one type of these SIT, 43 the Salmonella-induced filaments (SIF), is rather well-defined. However, the corresponding 44 host cell proteins are still poorly understood. To identify host factors required for the formation 45 of SCV and SIF, we performed a sub-genomic RNAi screen. The analyses comprised high-46 resolution live cell imaging to score effects on SIF induction, dynamics and morphology. The 47 hits of our functional RNAi screen comprise: i) The late endo-/lysosomal SNARE (soluble N-48 ethylmaleimide-sensitive factor attachment protein receptor) complex, consisting of STX7, 49 STX8, VTI1B, and VAMP7 or VAMP8, this is, in conjunction with RAB7 and the homotypic 50 fusion and protein sorting (HOPS) tethering complex, a complete vesicle fusion machinery. ii) 51 Novel interactions with the early secretory GTPases RAB1A and RAB1B, possibly providing 52 a link to coat protein complex I (COPI) vesicles and reinforcing recently identified ties to the 53 endoplasmic reticulum. iii) New connections to the late secretory pathway and/or the recycling 54 endosome via the GTPases RAB3A, RAB8A, and RAB8B and the SNAREs VAMP2, VAMP3, 55 and VAMP4. iv) An unprecedented involvement of clathrin-coated structures. The resulting set 56 of hits allowed to characterize completely new host factor interactions, and strengthen 57 observations from several previous studies. 58 Author Summary59 The facultative intracellular pathogen Salmonella enterica serovar Typhimurium induces the 60 reorganization of the endosomal system of mammalian host cells. This activity is dependent on 61 translocated effector proteins of the pathogen. The host cells factors required for endosomal 18.11.2019 Host factors for SIF formation 4 62 remodeling are only partially known. To identify such factors for formation and dynamics of 63 endosomal compartments in Salmonella-infected cell, we performed a live cell imaging-based 64 RNAi screen a to investigate the role of 496 mammalian proteins involved in cellular logistics. 65 We identified that endosomal remodeling by intracellular Salmonella dependent on host factors 66 in following functional classes: i) the late endo-/lysosomal SNARE (soluble N-ethylmaleimide-67 sensitive factor attachment protein receptor) complex, ii) the early secretory pathway, 68 represented by regulators GTPases RAB1A and RAB1B, iii) the late secretory pathway and/or 69 recycling endosomes represented by GTPases RAB3A, RAB8A, RAB8B, and the SNAREs 70 VAMP2, VAMP3, and VAMP4, and iv) clathrin-coated structures. The identification of these 71 new host factors provides further evidence ...

show abstract

“…138 Caspase-3 can degrade SipA to C-terminal and N-terminal: the C-terminal is responsible for actin polymerization and the N-terminal contains an SNARE motif. 139 The latter is responsible for the attachment and recurrence of host syntaxin 8 to SCV. SNARE is involved in endocytosis and syntaxin in rapid endocytosis and vesicle mobilization.…”

Section: Toxinsmentioning

confidence: 99%

Molecular Mechanisms of Salmonella Effector Proteins: A Comprehensive Review

Azimi¹,

Zamirnasta²,

Sani³

et al. 2020

IDR

View full text Add to dashboard Cite

Salmonella can be categorized into many serotypes, which are specific to known hosts or broadhosts. It makes no difference which one of the serotypes would penetrate the gastrointestinal tract because they all face similar obstacles such as mucus and microbiome. However, following their penetration, some species remain in the gastrointestinal tract; yet, others spread to another organ like gallbladder. Salmonella is required to alter the immune response to sustain its intracellular life. Changing the host response requires particular effector proteins and vehicles to translocate them. To this end, a categorized gene called Salmonella pathogenicity island (SPI) was developed; genes like Salmonella pathogenicity island encode aggressive or modulating proteins. Initially, Salmonella needs to be attached and stabilized via adhesin factor, without which no further steps can be taken. In this review, an attempt has been made to elaborate on each factor attached to the host cell or to modulating and aggressive proteins that evade immune systems. This review includes four sections: (A) attachment factors or T3SS-independent entrance, (B) effector proteins or T3SS-dependent entrance, (c) regulation of invasive genes, and (D) regulation of immune responses.

show abstract

Salmonella SipA mimics a cognate SNARE for host Syntaxin8 to promote fusion with early endosomes

Cited by 28 publications

References 75 publications

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

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

A trafficome-wide RNAi screen reveals deployment of early and late secretory host proteins and the entire late endo-/lysosomal vesicle fusion machinery by intracellularSalmonella

<p>Molecular Mechanisms of <em>Salmonella</em> Effector Proteins: A Comprehensive Review</p>

Contact Info

Product

Resources

About