Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Optimal translational fidelity is critical for Salmonella virulence and host interactions.

ABSTRACT: Translational fidelity is required for accurate flow of genetic information, but is frequently altered by genetic changes and environmental stresses. To date, little is known about how translational fidelity affects the virulence and host interactions of bacterial pathogens. Here we show that surprisingly, either decreasing or increasing translational fidelity impairs the interactions of the enteric pathogen Salmonella Typhimurium with host cells and its fitness in zebrafish. Host interactions are mediated by Salmonella pathogenicity island 1 (SPI-1). Our RNA sequencing and quantitative RT-PCR results demonstrate that SPI-1 genes are among the most down-regulated when translational fidelity is either increased or decreased. Further, this down-regulation of SPI-1 genes depends on the master regulator HilD, and altering translational fidelity destabilizes HilD protein via enhanced degradation by Lon protease. Our work thus reveals that optimal translational fidelity is pivotal for adaptation of Salmonella to the host environment, and provides important mechanistic insights into this process.

SUBMITTER: Fan Y

PROVIDER: S-EPMC6547416 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Parallel exploitation of diverse host nutrients enhances Salmonella virulence.

Project description:Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics, competitive infections, and computational approaches to obtain a comprehensive overview of Salmonella nutrition and growth in a mouse typhoid fever model. The data revealed that Salmonella accessed an unexpectedly diverse set of at least 31 different host nutrients in infected tissues but the individual nutrients were available in only scarce amounts. Salmonella adapted to this situation by expressing versatile catabolic pathways to simultaneously exploit multiple host nutrients. A genome-scale computational model of Salmonella in vivo metabolism based on these data was fully consistent with independent large-scale experimental data on Salmonella enzyme quantities, and correctly predicted 92% of 738 reported experimental mutant virulence phenotypes, suggesting that our analysis provided a comprehensive overview of host nutrient supply, Salmonella metabolism, and Salmonella growth during infection. Comparison of metabolic networks of other pathogens suggested that complex host/pathogen nutritional interfaces are a common feature underlying many infectious diseases.

| S-EPMC3636032 | biostudies-literature

Appropriate maturation and folding of 16S rRNA during 30S subunit biogenesis are critical for translational fidelity.

Project description:Ribosomal protein S5 is critical for small ribosomal subunit (SSU) assembly and is indispensable for SSU function. Previously, we identified a point mutation in S5, (G28D) that alters both SSU formation and translational fidelity in vivo, which is unprecedented for other characterized S5 mutations. Surprisingly, additional copies of an extraribosomal assembly factor, RimJ, rescued all the phenotypes associated with S5(G28D), including fidelity defects, suggesting that the effect of RimJ on rescuing the miscoding of S5(G28D) is indirect. To understand the underlying mechanism, we focused on the biogenesis cascade and observed defects in processing of precursor 16S (p16S) rRNA in the S5(G28D) strain, which were rescued by RimJ. Analyses of p16S rRNA-containing ribosomes from other strains further supported a correspondence between the extent of 5(') end maturation of 16S rRNA and translational miscoding. Chemical probing of mutant ribosomes with additional leader sequences at the 5(') end of 16S rRNA compared to WT ribosomes revealed structural differences in the region of helix 1. Thus, the presence of additional nucleotides at the 5(') end of 16S rRNA could alter fidelity by changing the architecture of 16S rRNA in translating ribosomes and suggests that fidelity is governed by accuracy and completeness of the SSU biogenesis cascade.

| S-EPMC2842029 | biostudies-literature

Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation.

Project description:Several pathogenic bacteria utilize type III secretion systems (TTSS) to deliver into host cells bacterial virulence proteins with the capacity to modulate a variety of cellular pathways. Once delivered into host cells, the accurate targeting of bacterial effectors to specific locations is critical for their proper function. However, little is known about the mechanisms these virulence effectors use to reach their subcellular destination. Here we show that the Salmonella TTSS effector proteins SspH2 and SseI are localized to the plasma membrane of host cells, a process dependent on S-palmitoylation of a conserved cysteine residue within their N-terminal domains. We also show that effector protein lipidation is mediated by a specific subset of host-cell palmitoyltransferases and that lipidation is critical for effector function. This study describes a remarkable mechanism by which a pathogen exploits host-cell machinery to properly target its virulence factors.

| S-EPMC4326042 | biostudies-literature

Digestive Biobank for Exploring Microbiota-host Interactions

Project description:Constitution of a biobank of tissues, whole blood and plasma samples and stools to identify markers associated with treatment response, postoperative morbidity including neuro-cognitive and mood complications and prognosis of Inflammatory Bowel disease or colorectal cancer.

| 6520 | ecrin-mdr-crc

Species-Specific Host-Virus Interactions: Implications for Viral Host Range and Virulence.

Project description:A growing number of studies indicate that host species-specific and virus strain-specific interactions of viral molecules with the host innate immune system play a pivotal role in determining virus host range and virulence. Because interacting proteins are likely constrained in their evolution, mutations that are selected to improve virus replication in one species may, by chance, alter the ability of a viral antagonist to inhibit immune responses in hosts the virus has not yet encountered. Based on recent findings of host-species interactions of poxvirus, herpesvirus, and influenza virus proteins, we propose a model for viral fitness and host range which considers the full interactome between a specific host species and a virus, resulting from the combination of all interactions, positive and negative, that influence whether a virus can productively infect a cell and cause disease in different hosts.

| S-EPMC6925338 | biostudies-literature

Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence.

Project description:Typhoidal and non-typhoidal Salmonelleae (NTS) cause typhoid fever and gastroenteritis, respectively, in humans. Salmonella typhoid toxin contributes to typhoid disease progression and chronic infection, but little is known about the role of its NTS ortholog. We found that typhoid toxin and its NTS ortholog induce different clinical presentations. The PltB subunit of each toxin exhibits different glycan-binding preferences that correlate with glycan expression profiles of host cells targeted by each bacterium at the primary infection or intoxication sites. Through co-crystal structures of PltB subunits bound to specific glycan receptor moieties, we show that they induce markedly different glycan-binding preferences and virulence outcomes. Furthermore, immunization with the NTS S. Javiana or its toxin offers cross-reactive protection against lethal-dose typhoid toxin challenge. Cumulatively, these results offer insights into the evolution of host adaptations in Salmonella AB toxins, their cell and tissue tropisms, and the design for improved typhoid vaccines and therapeutics.

| S-EPMC7292776 | biostudies-literature

Aspergillus fumigatus MedA governs adherence, host cell interactions and virulence.

Project description:In medically important fungi, regulatory elements that control development and asexual reproduction often govern the expression of virulence traits. We therefore cloned the Aspergillus fumigatus developmental modifier MedA and characterized its role in conidiation, host cell interactions and virulence. As in the model organism Aspergillus nidulans, disruption of medA in A. fumigatus dramatically reduced conidiation. However, the conidiophore morphology was markedly different between the two species. Further, gene expression analysis suggested that MedA governs conidiation through different pathways in A. fumigatus compared with A. nidulans. The A. fumigatusDeltamedA strain was impaired in biofilm production and adherence to plastic, as well as adherence to pulmonary epithelial cells, endothelial cells and fibronectin in vitro. The DeltamedA strain also had reduced capacity to damage pulmonary epithelial cells, and stimulate pro-inflammatory cytokine mRNA and protein expression. Consistent with these results, the A. fumigatusDeltamedA strain also exhibited reduced virulence in both an invertebrate and a mammalian model of invasive aspergillosis. Collectively, these results suggest that the downstream targets of A. fumigatus MedA mediate virulence, and may provide novel therapeutic targets for invasive aspergillosis.

| S-EPMC3370655 | biostudies-literature

EptC of Campylobacter jejuni mediates phenotypes involved in host interactions and virulence.

Project description:Campylobacter jejuni is a natural commensal of the avian intestinal tract. However, the bacterium is also the leading cause of acute bacterial diarrhea worldwide and is implicated in development of Guillain-Barré syndrome. Like many bacterial pathogens, C. jejuni assembles complex surface structures that interface with the surrounding environment and are involved in pathogenesis. Recent work in C. jejuni identified a gene encoding a novel phosphoethanolamine (pEtN) transferase, EptC (Cj0256), that plays a promiscuous role in modifying the flagellar rod protein, FlgG; the lipid A domain of lipooligosaccharide (LOS); and several N-linked glycans. In this work, we report that EptC catalyzes the addition of pEtN to the first heptose sugar of the inner core oligosaccharide of LOS, a fourth enzymatic target. We also examine the role pEtN modification plays in circumventing detection and/or killing by host defenses. Specifically, we show that modification of C. jejuni lipid A with pEtN results in increased recognition by the human Toll-like receptor 4-myeloid differentiation factor 2 (hTLR4-MD2) complex, along with providing resistance to relevant mammalian and avian antimicrobial peptides (i.e., defensins). We also confirm the inability of aberrant forms of LOS to activate Toll-like receptor 2 (TLR2). Most exciting, we demonstrate that strains lacking eptC show decreased commensal colonization of chick ceca and reduced colonization of BALB/cByJ mice compared to wild-type strains. Our results indicate that modification of surface structures with pEtN by EptC is key to its ability to promote commensalism in an avian host and to survive in the mammalian gastrointestinal environment.

| S-EPMC3553815 | biostudies-other

Contributions of Mass Spectrometry-Based Proteomics to Understanding Salmonella-Host Interactions.

Project description:As a model pathogen, Salmonella invades both phagocytic and non-phagocytic host cells and adopts an intracellular lifestyle in a membrane-bound compartment during infection. Therefore, a systemic overview of Salmonella adaptations to distinct host cells together with host remodeling will assist us in charting the landscape of host-pathogen interactions. Central to the Salmonella-host interplay are bacterial virulence factors (effectors) that are injected into host cells by type III secretion systems (T3SSs). Despite great progress, functional studies of bacterial effectors have experienced daunting challenges as well. In the last decade, mass spectrometry-based proteomics has evolved into a powerful technological platform that can quantitatively measure thousands of proteins in terms of their expression as well as post-translational modifications. Here, we will review the applications of high-throughput proteomic technologies in understanding the dynamic reprogramming of both Salmonella and host proteomes during the course of infection. Furthermore, we will summarize the progress in utilizing affinity purification-mass spectrometry to screen for host substrates of Salmonella T3SS effectors. Finally, we will critically discuss some limitations/challenges with current proteomic platforms in the context of host-pathogen interactions and highlight some emerging technologies that may offer the promise of tackling these problems.

| S-EPMC7400052 | biostudies-literature

Global mapping of Salmonella enterica-host protein-protein interactions during infection.

Project description:Intracellular bacterial pathogens inject effector proteins to hijack host cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32 Salmonella enterica serovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effectors and quantified PPIs in macrophages and epithelial cells. We identified 446 effector-host PPIs, 25 of which were previously described, and validated 13 by reciprocal co-immunoprecipitation. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. We demonstrate that SseJ, SseL, and SifA modulate cholesterol accumulation at the Salmonella-containing vacuole (SCV) partially via the cholesterol transporter Niemann-Pick C1 protein. PipB recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by phosphorylating formin-like proteins. This study provides a method for probing host-pathogen PPIs during infection and a resource for interrogating STm effector mechanisms.

| S-EPMC8561747 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data