Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mice ileal tissue in the presence of Listeria monocytogenes EGD-e and intestinal microbiota.

ABSTRACT: The higher susceptibility of the germ-free (GF) mice to bacterial infection has been proposed to be due to a lack of host immune defense. We hypothesized that this lower efficiency to mount a proficient defense might correlate with an aberrant miRNA expression, leading to the host failure to adapt its gene transcriptomic response to infection. To explore this hypothesis, we undertook a thorough transcriptional analysis of the host intestine in uninfected conventional (CV0) and germ-free (GF0) mice, by monitoring both the miRNA and mRNA expression levels. Crossing of the intestinal epithelial barrier is the first step of L. monocytogenes oral infection. Total eukaryotic RNAs were extracted from the ileum of uninfected conventional (CV0) and germ-free (GF0) mice and from L. monocytogenes infected conventional and germ-free mice 24h p.i (CV24 and GF24, respectively) and 72h p.i (CV72 and GF72, respectively). From these samples, transcriptome profiles were generated using Illumina sequencing for miRNA expression or microarrays for mRNA expression.

ORGANISM(S): Mus musculus

SUBMITTER: Christophe Becavin

PROVIDER: E-MTAB-1800 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The intestinal microbiota interferes with the microRNA response upon oral Listeria infection.

Archambaud Cristel C Sismeiro Odile O Toedling Joern J Soubigou Guillaume G Bécavin Christophe C Lechat Pierre P Lebreton Alice A Ciaudo Constance C Cossart Pascale P

mBio 20131210 6

<h4>Unlabelled</h4>The intestinal tract is the largest reservoir of microbes in the human body. The intestinal microbiota is thought to be able to modulate alterations of the gut induced by enteropathogens, thereby maintaining homeostasis. Listeria monocytogenes is the agent of listeriosis, an infection transmitted to humans upon ingestion of contaminated food. Crossing of the intestinal barrier is a critical step of the infection before dissemination into deeper organs. Here, we investigated th ...[more]

PMID: 24327339

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Project description:The cellular proteome is the set of expressed proteins at a given time and defines an organism's phenotype under specific conditions. The proteome is shaped and remodeled by both protein synthesis and degradation. In this study, we combined metabolic and chemical isobaric peptide labeling to simultaneously determine protein decay and de novo synthesis of intracellular Listeria monocytogenes, while focusing on the role of the AAA+ chaperone protein ClpC. ClpC associates with the peptidase ClpP to form an ATP-dependent protease complex and has been shown to play a role in virulence development in the human pathogen L. monocytogenes. However, the mechanism by which ClpC is involved in the survival and proliferation of intracellular L.monocytogenes remains elusive. We observed extensive proteome remodeling in L. monocytogenes upon interaction with the host, supporting the hypothesis that ClpC-dependent protein degradation is required to initiate bacterial adaptation mechanisms. We identified more than 100 putative ClpC target proteins through their stabilization in a clpC deletion strain. Beyond the identification of direct targets, we also observed indirect effects of the clpC deletion on the protein abundance in diverse cellular and metabolic pathways, such as iron acquisition and flagellar assembly. Overall, our data highlights the crucial role of ClpC for L. monocytogenes adaptation to the host environment through proteome remodeling. Importance Survival and proliferation of pathogenic bacteria inside the host depend on their ability to adapt to the changing environment. It is therefore important to profile the underlying changes on the bacterial proteome level during the infection process to understand pathogenesis and host-dependent adaptation processes. The interplay between protein synthesis and decay governs cellular protein abundance. SILAC pulse labeling enables direct readout of these events during infection. Combining this approach with tandem-mass-tag (TMT) labeling enabled multiplexed and time-resolved bacterial proteome quantification during infection. We applied this integrated approach to investigate protein turnover during the temporal progression of bacterial adaptation to the host on a system-wide scale. Our experimental approach can easily be transferred to probe the proteome remodeling in other bacteria under a variety of perturbations.

Dataset Information

Transcription profiling of mice ileal tissue in the presence of Listeria monocytogenes EGD-e and intestinal microbiota.

Publications

The intestinal microbiota interferes with the microRNA response upon oral Listeria infection.

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