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Series GSE104599 Query DataSets for GSE104599
Status Public on Apr 03, 2018
Title Gene Enrichment Analysis Reveals Major Regulators of Mycobacterium tuberculosis Gene Expression in Two Models of Antibiotic Tolerance
Organism Mycobacterium tuberculosis
Experiment type Expression profiling by high throughput sequencing
Summary The development of antibiotic tolerance is believed to be a major factor in the lengthy duration of current tuberculosis therapies. In the current study, we have modeled antibiotic tolerance in vitro by exposing Mycobacterium tuberculosis to two distinct stress conditions: progressive hypoxia and nutrient starvation [phosphate-buffered saline (PBS)]. We then studied the bacterial transcriptional response using RNA-seq and employed a bioinformatics approach to identify important transcriptional regulators, which was facilitated by a novel Regulon Enrichment Test (RET). A total of 17 transcription factor (TF) regulons were enriched in the hypoxia gene set and 16 regulons were enriched in the nutrient starvation, with 12 regulons enriched in both conditions. Using the same approach to analyze previously published gene expression datasets, we found that three M. tuberculosis regulons (Rv0023, SigH, and Crp) were commonly induced in both stress conditions and were also among the regulons enriched in our data. These regulators are worthy of further study to determine their potential role in the development and maintenance of antibiotic tolerance in M. tuberculosis following stress exposure.
Overall design Samples from 4 different conditions (7H9, PBS, Hypoxia, Phosphate-depleted) and 2 different strains (CDC1551, CDC1551-rpoB). Strain CDC1551-rpoB contains the H526D SNP in the rpoB gene. 2, 3, or 4 replicates per condition.
Contributor(s) Karakousis PC, Rifat D, Matern W
Citation(s) 29670589
Submission date Oct 04, 2017
Last update date Jul 25, 2021
Contact name Petros Constantine Karakousis
Phone 4105028233
Organization name Johns Hopkins University School of Medicine
Department Department of Infectious Diseases
Lab Center for TB Research
Street address 733 North Broadway
City Baltimore
State/province MD
ZIP/Postal code 21202
Country USA
Platforms (1)
GPL18768 Illumina HiSeq 2000 (Mycobacterium tuberculosis)
Samples (22)
GSM2803945 7H9_rep1
GSM2803946 7H9_rep2
GSM2803947 7H9_rep3
BioProject PRJNA413190
SRA SRP119427

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Supplementary file Size Download File type/resource
GSE104599_7H9vsPBS_low-read-rm.csv.gz 241.3 Kb (ftp)(http) CSV
GSE104599_7H9vshyp_low-read-rm.csv.gz 241.8 Kb (ftp)(http) CSV
GSE104599_RAW.tar 1.6 Mb (http)(custom) TAR (of RPKM)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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