Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

Lin, Zhijie; Zhang, Yong Guo; Xia, Yinglin; Xu, Xiulong; Jiao, Xinan; Sun, Jun

doi:10.1074/jbc.m116.757393

Cited by 49 publications

(43 citation statements)

References 59 publications

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“…Also stabilises intestinal tight junctions (Jones et al, 2008;Lin et al, 2016;Wu, Jones, & Neish, 2012) SlrP STM0800 t2087 a (STY0833) a SPA1952 a E3 ubiquitin ligase which mediates ubiquitination of mammalian thioredoxin and interacts with the chaperone ERdj3, leading to cell death (Bernal-Bayard, Cardenal-Muñoz, & Ramos-Morales, 2010;Bernal-Bayard & Ramos-Morales, 2009;Tsolis et al, 1999) (Continues) Absent Absent E3 ubiquitin ligase that interacts with the serine/threonine protein kinase PKN1 and inhibits NF-κB signalling (Haraga & Miller, 2003 SteA STM1583 t1493 (STY1482) SPA1285 Binds to phosphatidylinositol 4-phosphate (PI(4)P), localizes to SCV membranes and to Sifs. Also stabilises intestinal tight junctions (Jones et al, 2008;Lin et al, 2016;Wu, Jones, & Neish, 2012) SlrP STM0800 t2087 a (STY0833) a SPA1952 a E3 ubiquitin ligase which mediates ubiquitination of mammalian thioredoxin and interacts with the chaperone ERdj3, leading to cell death (Bernal-Bayard, Cardenal-Muñoz, & Ramos-Morales, 2010;Bernal-Bayard & Ramos-Morales, 2009;Tsolis et al, 1999) (Continues) Absent Absent E3 ubiquitin ligase that interacts with the serine/threonine protein kinase PKN1 and inhibits NF-κB signalling (Haraga & Miller, 2003 SteA STM1583 t1493 (STY1482) SPA1285 Binds to phosphatidylinositol 4-phosphate (PI(4)P), localizes to SCV membranes and to Sifs.…”

Section: Stm4157mentioning

confidence: 99%

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

Johnson

Mylona

Frankel

2018

Cellular Microbiology

141

106

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Although nontyphoidal Salmonella (NTS; including Salmonella Typhimurium) mainly cause gastroenteritis, typhoidal serovars (Salmonella Typhi and Salmonella Paratyphi A) cause typhoid fever, the treatment of which is threatened by increasing drug resistance. Our understanding of S. Typhi infection in human remains poorly understood, likely due to the host restriction of typhoidal strains and the subsequent popularity of the S. Typhimurium mouse typhoid model. However, translating findings with S. Typhimurium across to S. Typhi has some limitations. Notably, S. Typhi has specific virulence factors, including typhoid toxin and Vi antigen, involved in symptom development and immune evasion, respectively. In addition to unique virulence factors, both typhoidal and NTS rely on two pathogenicity-island encoded type III secretion systems (T3SS), the SPI-1 and SPI-2 T3SS, for invasion and intracellular replication. Marked differences have been observed in terms of T3SS regulation in response to bile, oxygen, and fever-like temperatures. Moreover, approximately half of effectors found in S. Typhimurium are either absent or pseudogenes in S. Typhi, with most of the remaining exhibiting sequence variation. Typhoidal-specific T3SS effectors have also been described. This review discusses what is known about the pathogenesis of typhoidal Salmonella with emphasis on unique behaviours and key differences when compared with S. Typhimurium.

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Section: Stm4157mentioning

confidence: 99%

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

Johnson

Mylona

Frankel

2018

Cellular Microbiology

141

106

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“…In the current study, we report that the S. Enteritidis effector protein AvrA decreased Beclin-1 protein expression, thus impairing the autophagic response, for the benefit of The AvrA from S. Typhimurium is known as an anti-inflammatory effector that possesses acetyltransferase activity toward specific host MAPKKs and inhibits the host JNK/c-Jun/AP-1 and NF-κB pathways, but the role of AvrA from S. Enteritidis is less explored (9,(24)(25)(26)(27)(28). Here, we demonstrated that S. Enteritidis AvrA inhibited the autophagic response.…”

Section: Discussionmentioning

confidence: 80%

“…Beclin-1 is regulated by the JNK signaling pathway (30). Previous studies have shown that Salmonella AvrA inhibits the activation of the JNK signaling pathways (9,28). Using Western blotting, we found that the protein levels of p-JNK and p-c-Jun were higher in the S.E-AvrA --infected cells than in the cells infected by the S.E-WT or S.E-AvrA + strains (Fig.…”

Section: Avra Reduces Beclin-1 At the Protein Levels And Interacts Wimentioning

confidence: 70%

“…Through these methods, AvrA inhibits the host inflammatory response and stabilizes the intestinal tight junctions to the benefit of bacterial survival (9,(24)(25)(26)(27)(28). However, the role of AvrA in Salmonella infection and host autophagic response is unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we hypothesize that Salmonella Enteritidis effector AvrA inhibits the autophagic response by decreasing Beclin-1 expression. We used wild-type, Salmonella Enteritidis C50336 and established a deletion Salmonella Enteritidis mutant S.E-AvrAand a plasmid-mediated complementary strain S.E-AvrA -/pAvrA + (S.E-AvrA + ) (28). In cell cultures, organoids and infected mice, we explored the physiologically related effects and molecular mechanism of AvrA regulation of autophagy in intestinal epithelial cells, whereas most studies on bacterial effectors and autophagy only use cell cultures.…”

Section: Introductionmentioning

confidence: 99%

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SalmonellaEnteritidis Effector AvrA suppresses autophagy by reducing Beclin-1 protein

Jiao

Zhang

Lin

et al. 2020

Preprint

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Autophagy is a cellular process to clear pathogens. Salmonella enterica serovar Enteritidis (S.E) has emerged as one of the most important food-borne pathogens.However, major studies still focus on Salmonella enterica serovar Typhimurium. Here, we reported that AvrA, a S. Enteritidis effector, inhibited autophagy to promote bacterial survival in the host. We found that AvrA regulates the conversion of LC3 I into LC3 II and the enrichment of lysosomes. Beclin-1, a key molecular regulator of autophagy, was decreased after AvrA expressed strain colonization. In S.E-AvrA--infected cells, we found the increases of protein levels of p-JNK and p-c-Jun and the transcription level of AP-1. AvrA-reduction of Beclin-1 protein expression is through the JNK pathway. The JNK inhibitor abolished the AvrA-reduced Beclin-1 protein expression. Moreover, we identified that the AvrA mutation C186A abolished its regulation of Beclin-1 expression.In addition, AvrA protein interacted with Beclin-1. In organoids and infected mice, we explored the physiologically related effects and mechanism of AvrA in reducing Beclin-1 through the JNK pathway, thus attenuating autophagic responses. Importance:Salmonella Enteritidis is an important pathogen with a public health concern and farm production risk, yet the host-pathogen interactions that govern the survival of S.Enteritidis infections are incompletely understood. Anti-bacterial autophagy provides potent cell-autonomous immunity against bacterial colonization. Here, we report that a new role for effector AvrA of S. Enteritidis in the reduction of Beclin-1 protein expression through the JNK pathway and the attenuation of the autophagic response in intestinal epithelial cells. This finding not only indicates an important role of S. Enteritidis effector in reducing host protein as a strategy to suppress autophagy, but also suggests manipulating autophagy as a new strategy to treat infectious diseases.3

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Modulation of Intestinal Paracellular Transport by Bacterial Pathogens

Roxas

Viswanathan

2018

Comprehensive Physiology

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The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018.

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Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via the JNK Pathway

Cited by 49 publications

References 59 publications

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

TyphoidalSalmonella: Distinctive virulence factors and pathogenesis

SalmonellaEnteritidis Effector AvrA suppresses autophagy by reducing Beclin-1 protein

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens

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