Salmonella, E. coli, and Citrobacter Type III Secretion System Effector Proteins that Alter Host Innate Immunity

Qaidi, Samir El; Wu, Miaomiao; Zhu, Congrui; Hardwidge, Philip R.

doi:10.1007/5584_2018_289

Cited by 4 publications

(2 citation statements)

References 109 publications

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“…Studies suggest that the A/E pedestal formation contributes to bacterial pathogenesis (Miner & Rauch, 2024). Injected effectors also contribute to bacterial colonization and pathogenesis by hijacking and subverting host cell signaling and membrane trafficking pathways, targeting various organelles, and modulating cell death and innate immunity (El Qaidi et al, 2019; Lee et al, 2024; Shenoy et al, 2018). One such effector is EspH.…”

Section: Introductionmentioning

confidence: 99%

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Nandi,

Ramachandran,

Shalev

et al. 2024

Preprint

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EnteropathogenicE. coli(EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulent proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues. Mutating these sites abolished the EspH ability to inhibit the Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.

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Section: Introductionmentioning

confidence: 99%

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Nandi,

Ramachandran,

Shalev

et al. 2024

Preprint

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show abstract

“…S. Typhimurium invades the gastrointestinal tract through oral ingestion of contaminated food or water ( Pocsfalvi et al, 2016 ). Salmonella secretes proteins through specific secretion systems and these secreted proteins act as virulence factors (also known as effector proteins) to invade and regulate various functions of host cells, including inhibiting host immune responses ( Qaidi et al, 2018 ), promoting the survival of intracellular bacteria ( Haraga et al, 2008 ), and plasma membrane transport of target products ( Santos et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Label-free relative quantitative proteomics reveals extracellular vesicles as a vehicle for Salmonella effector protein delivery

Zhang

et al. 2022

Front. Microbiol.

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Extracellular vesicles are small vesicles with a diameter of 30–150 nm that are actively secreted by eukaryotic cells and play important roles in intercellular communication, immune responses, and tumorigenesis. Previous studies have shown that extracellular vesicles are involved in the process of Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. However, changes in the protein content of extracellular vesicles elicited by S. Typhimurium infection have not been determined. Here, we extracted the extracellular vesicles with high purity from S. Typhimurium-infected Henle-407 cells, a kind of human intestinal epithelial cells, by ultracentrifugation combined with an extracellular vesicles purification kit, and analyzed their protein composition using label-free relative quantitative proteomics. The extracted extracellular vesicles exhibited an oval vesicular structure under electron microscopy, with a mean diameter of 140.4 ± 32.4 nm. The exosomal marker proteins CD9, CD63, and HSP70 were specifically detected. Compared with the uninfected group, nearly 1,234 specifically loaded proteins were uncovered in S. Typhimurium-infected Henle-407 cells. Among them were 409 S. Typhimurium-derived specific proteins, indicating a significant alteration in protein composition of extracellular vesicles by S. Typhimurium infection. Notably, these proteins included 75 secretory proteins and over 300 non-secretory proteins of S. Typhimurium, implicating novel pathways for bacterial protein delivery, although it remains unclear if their loading into extracellular vesicles is active or passive. To investigate the roles of these extracellular proteins, we exemplified the function of SopB, a well-known T3SS effector protein, and showed that the extracellular SopB could be taken up by RAW264.7 macrophages, activating the phosphorylation of Akt. This study provides new insights into the mechanism of Salmonella infection through extracellular vesicles that transport virulence proteins to uninfected neighboring cells to facilitate further infection.

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EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases*

Nandi,

Ramachandran,

Shalev

et al. 2024

Gut Microbes

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Salmonella, E. coli, and Citrobacter Type III Secretion System Effector Proteins that Alter Host Innate Immunity

Cited by 4 publications

References 109 publications

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases

Label-free relative quantitative proteomics reveals extracellular vesicles as a vehicle for Salmonella effector protein delivery

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases*

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