Impact of<i>Salmonella enterica</i>Type III Secretion System Effectors on the Eukaryotic Host Cell

Ramos‐Morales, Francisco

doi:10.5402/2012/787934

Cited by 81 publications

(79 citation statements)

References 368 publications

(507 reference statements)

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“…The T3SS offers an interest as target for the design of new antibiotics [2]. However, another therapeutic approach consists in targeting the secreted effectors that, once delivered by the T3SS, play critical roles in manipulating the host cell to allow for bacterial invasion, intracellular survival and proliferation [3,4]. The nature of the effectors is very variable [5,6] and they utilize three main strategies to modify host cell function [7]: they directly bind to, covalently modify, or mimic endogenous host cell proteins.…”

Section: Introductionmentioning

confidence: 99%

The structure of the Slrp–Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family

Zouhir

Bernal-Bayard

Cordero-Alba

et al. 2014

Biochemical Journal

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Salmonella infections are a leading cause of bacterial foodborne illness in the United States and the European Union. Antimicrobial therapy is often administered to treat the infection but increasing isolates are being detected that demonstrate resistance to multiple antibiotics. Salmonella enterica contains two virulence related type-III secretion systems (T3SS): one promotes invasion of the intestine and the other one mediates systemic disease. Both of them secrete the SlrP protein acting as E3 ubiquitin ligase in human host cells where it targets thioredoxin-1 (Trx1). SlrP belongs to the NEL family of bacterial E3 ubiquitin ligases that have been observed in two distinct autoinhibitory conformations. We solved the 3D structure of the SlrP/Trx1 complex and determined the Trx1 ubiquitination site. The description of the substrate-binding mode sheds light on the first step of the activation mechanism of SlrP. Comparison with the available structural data of other NEL effectors allowed us to gain new insights into their autoinhibitory mechanism. We propose a molecular mechanism for the regulation of SlrP in which structural constraints sequestrating the NEL domain would be sequentially released. This work thus constitutes a new milestone in the understanding of how these T3SS effectors influence pathogen virulence. It also provides the fundamental basis for future development of new antimicrobials.

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Section: Introductionmentioning

confidence: 99%

The structure of the Slrp–Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family

Zouhir

Bernal-Bayard

Cordero-Alba

et al. 2014

Biochemical Journal

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“…enterica injects more than thirty T3SS effectors to their host cells and some of them have been shown to manipulate cellular processes such as actin cytoskeleton organization, tight junction alterations, biogenesis of the Salmonella-containing vacuole and cell death [6].…”

Section: Introductionmentioning

confidence: 99%

Global impact of Salmonella type III secretion effector SteA on host cells

Cardenal‐Muñoz

Gutiérrez

Ramos‐Morales

2014

Biochemical and Biophysical Research Communications

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Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell-cell adhesion and migration.

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“…Sensing the acidification of the vacuole, Salmonella then deploys the SPI-2 secretion system, which delivers another set of effectors into the host cytoplasm. Broadly, these effectors are responsible for remodelling the vacuole into a replication-permissive space (Figure 3), translocating and extending the vacuole along host microtubules, and interfering with the secretion of inflammatory cytokines 22,23 . Together, these activities enable Salmonella to survive within both epithelia and phagocytic cells, to replicate to high numbers, and to disseminate to adjacent cells and on to new hosts.…”

Section: Salmonella Subverts Host Cells To Achieve Infectionmentioning

confidence: 99%

Salmonella in Australia: understanding and controlling infection

Newson¹

2017

Microbiol. Aust.

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The bacterium Salmonella causes a spectrum of foodborne diseases ranging from acute gastroenteritis to systemic infections, and represents a significant burden of disease globally. In Australia, Salmonella is frequently associated with outbreaks and is a leading cause of foodborne illness, which results in a significant medical and economic burden. Salmonella infection involves colonisation of the small intestine, where the bacteria invades host cells and establishes an intracellular infection. To survive within host cells, Salmonella employs type-three secretion systems to deliver bacterial effector proteins into the cytoplasm of host cells. These bacterial effectors seek out and modify specific host proteins, disrupting host processes such as cell signalling, intracellular trafficking, and programmed cell death. This strategy of impairing host cells allows Salmonella to establish a replicative niche within the cell, where they can replicate to high numbers before escaping to infect neighbouring cells, or be transmitted to new hosts. While the importance of effector protein translocation to infection is well established, our understanding of many effector proteins remains incomplete. Many Salmonella effectors have unknown function and unknown roles during infection. A greater understanding of how Salmonella manipulates host cells during infection will lead to improved strategies to prevent, control, and eliminate disease. Further, studying effector proteins can be a useful means for exploring host cell biology and elucidating the details of host cell signalling.

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Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Cited by 81 publications

References 368 publications

The structure of the Slrp–Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family

The structure of the Slrp–Trx1 complex sheds light on the autoinhibition mechanism of the type III secretion system effectors of the NEL family

Global impact of Salmonella type III secretion effector SteA on host cells

Salmonella in Australia: understanding and controlling infection

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