Hypoxia is NOT THE MAIN stress When M. tuberculosis is in a dormancy-LIKE FATTY ACID environment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA488546 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7768614.fastq.gz | Fastqsanger.gz | |||
| SRR7768615.fastq.gz | Fastqsanger.gz | |||
| SRR7768616.fastq.gz | Fastqsanger.gz | |||
| SRR7768617.fastq.gz | Fastqsanger.gz |
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Project description:The capacity of Mycobacterium tuberculosis (Mtb) to sense, respond and adapt to variable and hostile environment within the host, has made it one of the most successful human pathogens. During different stages of infection, the bacillus is surrounding by a plethora of lipid rich molecules and current evidence points out the relevance of fatty acids during the Mtb infectious process. In this study, we have compared the transcriptional response of Mtb to hypoxia in cultures grown in both, a mix of even long-chain fatty acids and dextrose as carbon sources. Using RNA sequencing, we have identified the differential expressed genes in early and late hypoxia defined according to the in vitro Wayne model and compared the results with the exponential phase of growth in both carbon sources. Our results showed that, different to dextrose, the number of genes overexpressed in hypoxia in the lipid medium was quite low in both, early and late hypoxia in all functional categories describes for Mtb. The exception were the transcripts of stable and non-coding RNAs which were more expressed in the fatty acid medium. We found that SigB and SigE were overexpressed in the early phase of hypoxia, confirming their pivotal role in early adaptation to low oxygen concentration independently of the carbon source. A drastic contrast was found with the transcriptional regulatory factors at early hypoxia. Only 2 transcriptional factors were overexpressed in early hypoxia in the lipid medium compared to 37 that were overexpressed in the dextrose medium. Instead of Rv0081, known to be the central regulator of hypoxia in dextrose, Rv2745c, (ClgR), is playing a main role in hypoxia in the fatty acids medium. The low level of genes associated to stress-response, showed by Mtb during their adaptation to hypoxia in fatty acids, suggested that this lipid environment makes hypoxia a less stressful condition for the tubercle bacilli. Therefore, when the bacillus is surviving in that environment, its metabolism seemed to be already adapted to different stresses within the host, including hypoxia. This fact could explain the success of Mtb to establish long-term survival during latent infection.
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2011-04-21 | E-GEOD-28747 | biostudies-arrayexpress
Project description:The capacity of Mycobacterium tuberculosis (Mtb) to sense, respond and adapt to a variable and hostile environment within the host makes it one of the most successful human pathogens. During different stages of infection, Mtb is surrounded by a plethora of lipid molecules and current evidence points out the relevance of fatty acids during the infectious process. In this study, we have compared the transcriptional response of Mtb to hypoxia in cultures supplemented with a mix of even long-chain fatty acids or dextrose as main carbon sources. Using RNA sequencing, we have identified differential expressed genes in early and late hypoxia, defined according to the in vitro Wayne and Hayes model, and compared the results with the exponential phase of growth in both carbon sources. We show that the number of genes over-expressed in the lipid medium was quite low in both, early and late hypoxia, relative to conditions including dextrose, with the exception of transcripts of stable and non-coding RNAs, which were more expressed in the fatty acid medium. We found that sigB and sigE were over-expressed in the early phase of hypoxia, confirming their pivotal role in early adaptation to low oxygen concentration independently of the carbon source. A drastic contrast was found with the transcriptional regulatory factors at early hypoxia. Only 2 transcriptional factors were over-expressed in early hypoxia in the lipid medium compared to 37 that were over-expressed in the dextrose medium. Instead of Rv0081, known to be the central regulator of hypoxia in dextrose, Rv2745c (ClgR), seems to play a main role in hypoxia in the fatty acid medium. The low level of genes associated to the stress-response during their adaptation to hypoxia in fatty acids, suggests that this lipid environment makes hypoxia a less stressful condition for the tubercle bacilli. Taken all together, these results indicate that the presence of lipid molecules shapes the metabolic response of Mtb to an adaptive state for different stresses within the host, including hypoxia. This fact could explain the success of Mtb to establish long-term survival during latent infection.
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Project description:These data represent the expression patterns of Mycobacterium tuberculosis in progressive hypoxia, nutrient depletion, and in-vivo hollow fiber models of dormancy. The assumptions are that the set of genes that respond to INH treatment during Log phase growth would not be differentially regulated during INH treatment in the dormancy models, and that the overall number of differentially regulated genes would be reduced do to the low metabolic state of the cells. Keywords: Dormancy Model Drug Response Comparison
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