Effect of hypoxia on Mycobacterium tuberculosis-host phagocyte interactions
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta
SUBMITTER: Smriti Mehra
PROVIDER: E-GEOD-47163 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The Rv2745c (clgR) gene encodes a Clp protease gene regulator that is induced in response to a variety of stress conditions and potentially plays a role in Mtb pathogenesis. The isogenic Mtb:ΔRv2745c mutant is significantly more sensitive to in vitro redox stress generated by diamide, relative to wild-type Mtb, implicating a role for ClgR in the management of intraphagosomal redox stress. Redox stress led to dysregulation of the σH regulon in the isogenic mutant, Mtb:ΔRv2745c. Induction of clgR in Mtb and Mtb:ΔRv2745c (comp) did not lead to Clp protease induction, indicating that clgR has additional functions that need to be elucidated. Disruption of genes involved in sulfate assimilation also occurred in the knock out, implicating clgR as a possible regulator of downstream signaling cascades that facilitate Mtb survival. At different time points, (30, 60 and 90 mins, t=30, t=60 and t=90) following the addition of diamide to M. tuberculosis CDC1551 cultures, RNA was extracted and labeled with Cy5. RNA was also extracted from pre-diamide addition (t=0) time points and labeled with Cy3. These samples were cohybridized on M. tuberculosis CDC1551 whole genome microarrays using biological triplicate samples (i.e. samples derived from three distinct cultures and treatments) and thus three unique datasets were generated for each of the three time points for Mtb. Similar experiments were performed for an isogenic Rv2745c (clgR) mutant in Mtb CDC1551 which was generated by allelic exchange and a complemented strain which was generated by trans-complementation of Rv2745c in the attB locus of the mutant strain, thus restoring the wild type regulation of Rv2745c.
2014-03-25 | E-GEOD-55817 | biostudies-arrayexpress
Project description:The isogenic Mtb:ΔRv2745c mutant is significantly more sensitive normoxia conditions after a period of hypoxia, relative to wild-type Mtb, implicating a role for ClgR in response to reactivation, in vivo. Both hypoxia and reaeration treatment led to dysregulation of the σH regulon in the isogenic mutant, Mtb:ΔRv2745c. Induction of clgR in Mtb did lead to Clp protease induction, indicating that clgR plays a role in differntially activating downstream genes in a condition dependent manner. Disruption of genes involved in the dosR regulon, the Enduring Hypoxia Response, lipid synthesis, and mycolic acid synthesis also occurred in the knock out, implicating clgR as a possible regulator of downstream signaling cascades that facilitate Mtb survival. There was also a differnetial response of genes that are known Clp protease targets, in addition to potential Clp protease targets that had similar induction patterns as known Clp protease targets. At different time points, following hypoxia (day 1, day 5, and day 7) and reaeration (1 hour, 4 hour, 6 hour, 12 hour, 24 hour, and 48 hour) treatments M. tuberculosis CDC1551 cultures, RNA was extracted and labeled with Cy5. RNA was also extracted from pre-hypoxia (t=0) time points and labeled with Cy3. These samples were cohybridized on M. tuberculosis CDC1551 whole genome microarrays using biological triplicate samples (i.e. samples derived from three distinct cultures and treatments) and thus three unique datasets were generated for each of the three time points for Mtb. Similar experiments were performed for an isogenic Rv2745c (clgR) mutant in Mtb CDC1551 which was generated by allelic exchange.
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Project description:The planktonic versus biofilm gene expression arrays were performed in a/alpha cell types. Gene expression arrays were performed on planktonic vs biofilm cells grown in Spider medium at 37C. Normalized data is reported in matrix. Biofilm strains (48 hour biofilms) were compared to planktonic strains (log phase planktonic cells) in Spider medium at 37C.
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Project description:DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness. DNA methylome analysis of pooled Human, Chimpanzee and Macaque
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