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| Status |
Public on Oct 19, 2022 |
| Title |
Host metabolic reprogramming during immune activation promotes intracellular bacterial survival (host and bacteria) |
| Organisms |
Mus musculus; Salmonella enterica subsp. enterica serovar Typhimurium |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Intracellular pathogens, such as Salmonella enterica serovar Typhimurium (S.Tm), are able to sense and respond to a changing host cell environment. Macrophages exposed to microbial products undergo metabolic changes that are increasingly understood to drive a productive inflammatory response. However, the role of macrophage metabolic reprogramming in bacterial adaptation to the intracellular environment has not been explored. Here we show that changes in host metabolic state serve as a signal detected byS.Tm. Using metabolic profiling and dual RNA-seq, we show that succinate accumulates in infected macrophages and is sensed by intracellular S.Tm to promote induction of virulence genes. Succinate uptake by the bacterium drives induction of pmrAB-dependent genes and SPI-2 virulence-associated regulon. S.Tm lacking the DcuB transporter for succinate uptake display impaired intracellular survival. Our work demonstrates that accumulation of metabolic intermediates, necessary for macrophage activation, promote intracellular survival of pathogens, opening a new realm of metabolic host-pathogen crosstalk.
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| Overall design |
DualSeq data. 18 Mus musculus samples (control, manZ, and WT bacteria, with or without 2-DG at 0.5h, 6h and 24h post-infection) in triplicates. 12 Salmonella enterica serovar Typhimurium samples (manZ and WT bacteria, with or without 2-DG at 0.5h, 6h and 24h posut-infection) in triplicates.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/33479153/
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| Contributor(s) |
Rosenberg G, Yehezkel D, Nissani N, Hen-Avivi S, Brenner S, Itkin M, Malitsky S, Bossel Ben-Moshe N, Avraham R |
| Citation(s) |
33479153 |
| |
| Submission date |
Oct 21, 2019 |
| Last update date |
Jan 19, 2023 |
| Contact name |
Roi Avraham |
| E-mail(s) |
roi.avraham@weizmann.ac.il
|
| Organization name |
Weizmann Institute of Science
|
| Street address |
Herzl St 234
|
| City |
Rehovot |
| ZIP/Postal code |
7610001 |
| Country |
Israel |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24107 |
Illumina NextSeq 500 (Mus musculus; Salmonella enterica subsp. enterica serovar Typhimurium) |
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| Samples (54)
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| This SubSeries is part of SuperSeries: |
| GSE139208 |
Host succinate is a signal for activation of Salmonella virulence during intracellular infection |
|
| Relations |
| BioProject |
PRJNA578744 |
| SRA |
SRP226510 |
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