Evaluation of induced cellular cytokine profile in response to Rifampin-mono resistant Mycobacterium tuberculosis strain
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PROVIDER: PRJNA475416 | ENA |
REPOSITORIES: ENA
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Project description:Comparing of induced cellular cytokine profile in response to Rifampin-mono resistant and H37Rv Mycobacterium tuberculosis strains
2018-06-11 | GSE115546 | GEO
Project description:Rifampin causes drug interactions by altering hepatic drug metabolism. Because microRNAs (miRNAs) have been shown to regulate genes involved in drug metabolism, we determined the effect of rifampin on the expression of hepatic miRNAs. Primary human hepatocytes from seven subjects were treated with rifampin, and the expression of miRNA and cytochrome P450 (P450) mRNAs was measured by TaqMan assays and RNA-seq, respectively. Rifampin induced the expression of 10 clinically important and 13 additional P450 genes and repressed the expression of 9 other P450 genes (P < 0.05). Rifampin induced the expression of 33 miRNAs and repressed the expression of 35 miRNAs (P < 0.05). Several of these changes were highly negatively correlated with the rifampin-induced changes in the expression of their predicted target P450 mRNAs, supporting the possibility of miRNA-induced regulation of P450 mRNA expression. In addition, several other miRNA changes were positively correlated with the changes in P450 mRNA expression, suggesting similar regulatory mechanisms. Despite the interindividual variability in the rifampin effects on miRNA expression, principal components analysis clearly separated the rifampin-treated samples from the controls. In conclusion, rifampin treatment alters miRNA expression patterns in human hepatocytes, and some of the changes were correlated with the rifampin-induced changes in expression of the P450 mRNAs they are predicted to target. Primary human hepatocytes were treated rifampin or vehicle for 24 hours. Rifampin-treated samples are not available for the 30Jul10 patient or the Hep2 patient due to raw data file corruption.
2016-04-06 | E-GEOD-79933 | biostudies-arrayexpress
Project description:Rifampin causes drug interactions by altering hepatic drug metabolism. Because microRNAs (miRNAs) have been shown to regulate genes involved in drug metabolism, we determined the effect of rifampin on the expression of hepatic miRNAs. Primary human hepatocytes from seven subjects were treated with rifampin, and the expression of miRNA and cytochrome P450 (P450) mRNAs was measured by TaqMan assays and RNA-seq, respectively. Rifampin induced the expression of 10 clinically important and 13 additional P450 genes and repressed the expression of 9 other P450 genes (P < 0.05). Rifampin induced the expression of 33 miRNAs and repressed the expression of 35 miRNAs (P < 0.05). Several of these changes were highly negatively correlated with the rifampin-induced changes in the expression of their predicted target P450 mRNAs, supporting the possibility of miRNA-induced regulation of P450 mRNA expression. In addition, several other miRNA changes were positively correlated with the changes in P450 mRNA expression, suggesting similar regulatory mechanisms. Despite the interindividual variability in the rifampin effects on miRNA expression, principal components analysis clearly separated the rifampin-treated samples from the controls. In conclusion, rifampin treatment alters miRNA expression patterns in human hepatocytes, and some of the changes were correlated with the rifampin-induced changes in expression of the P450 mRNAs they are predicted to target.
2016-04-06 | GSE79933 | GEO
Project description:This study investigates the role of the phosphate-specific transport system gene pstA1 in rifampin tolerance in Mycobacterium tuberculosis. We constructed a pstA1 deletion mutant (ΔpstA1) and demonstrated that it exhibits enhanced rifampin susceptibility compared to wild-type H37Rv. To explore the molecular mechanisms underlying this phenotype, we performed RNA-seq transcriptomic analysis comparing wild-type and ΔpstA1 strains grown in standard Middlebrook 7H9 broth under exposure to sub-inhibitory rifampin (7.5 ng/ml, 1/4 MIC) for 30 or 60 minutes. The analysis revealed substantial transcriptional reprogramming in ΔpstA1, providing insights into how loss of PstA1 function leads to increased rifampin susceptibility.
2025-11-27 | GSE310692 | GEO
Project description:Many clinically relevant bacterial pathogens are encapsulated, as exemplified by Salmonella enterica serovar Typhi. S. Typhi, the causative agent of the life-threatening systemic disease enteric fever, expresses Vi as the outermost surface glycan that protects the bacteria from host immune responses. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi strains, as well as Vi variants, are widespread globally. Our WGS analyses indicate that almost all S. Typhi clinical isolates are susceptible to rifamycins and azithromycin. Rifampin, even at sub-MIC levels, eliminates the protective capsule Vi, a process referred to as ‘decapsulation’, thereby enhancing bacterial clearance. Antibiotic-mediated decapsulation of S. Typhi appears specific to rifamycins, since azithromycin does not decapsulate S. Typhi. Rifampin mediated decapsulation occurs at the transcriptional level, where both high AT content and specific RpoB residues play a crucial role. Rifampin also effectively decapsulates Vi variants, which accounts for 1 in 5 S. Typhi isolates at the global level. A mechanistic explanation for rifampin mediated decapsulation of S. Typhi appears to be applicable to other encapsulated pathogens, including S. Paratyphi C.
2025-05-15 | GSE295448 | GEO
Project description:BackgroundAlthough relatively rare, rifampin mono-resistant tuberculosis (RMR TB) poses important challenges to effective TB treatment and control. Information on the burden of RMR TB and treatment outcomes is needed to inform diagnosis and management.MethodsStandardized variables were collected from the New York City (NYC) tuberculosis surveillance system for patients treated for RMR TB in NYC during 2010-2021.ResultsOf 7097 TB cases reported in 2010-2021, 31 (<1%) were treated clinically as RMR TB. Five (16%) of these patients had HIV. Seventeen patients (55%) had TB that was rifampin-resistant by both molecular and phenotypic drug susceptibility testing; 2 (6%) had rifampin resistance by phenotypic tests, and molecular tests were not done; and 12 (39%) were identified based only on molecular tests. Among these 12, 7 were rifampin-sensitive by phenotypic tests, and phenotypic testing could not be done for the other 5. Ten of the 31 (32%) were diagnosed in 2010-2015; the other 21 (including 10/12 diagnosed by molecular tests alone) were diagnosed in 2016-2021. Of the 31 patients, 21 (68%) completed treatment (median treatment duration of 18 months). Although the interval between tuberculosis treatment initiation and change to a non-rifamycin-containing regimen decreased significantly during the study period, the overall duration of treatment did not decrease significantly between 2010 and 2021.ConclusionsMolecular drug susceptibility tests identified cases of RMR TB that were not detected by phenotypic testing and helped enable timely adjustment of tuberculosis treatment regimens. Short-course regimens are needed to reduce duration of treatment for RMR TB.
| S-EPMC10662657 | biostudies-literature
Project description:We report the application of next generation sequencing technology for high-throughput profiling of total RNA to determine the expression of all genes expressed in human primary hepatocytes derived from three healthy (drug/tobacco/alcohol free) volunteers in response to anti-tuberculosis antibiotics, including, rifampin, rifabutin and rifapentine through comparison with gene profiles of vehicle (methanol) treated and untreated cells. We determined the response of over 22,000 genes expressed in human primary hepatocytes following rifampin, rifabutin and rifapentine treatment for 72h. We found that several drug metabolizing enzymes, including cytochrome P450 3A4 and drug transporters are differentially expressed in human primary hepatocytes in response to rifamycin antibiotics. We utilized the information generated with differential gene expression study to determine interaction of rifamyicn antibiotics with antiviral, antibacterial, antifungal agents and other drugs used to treat several ailments in tuberculosis patients. This study provides a comprehensive profiles of genes expressed in response to rifamycin antibiotics towards characterization of their drug interactions with the drugs that are combined to treat various viral, bacterial, fungal and other diseases, including cancer.
2020-03-26 | GSE139896 | GEO
Project description:Rifampin-resistant meningococcal disease occurred in a child who had completed rifampin chemoprophylaxis for exposure to a sibling with meningococcemia. Susceptibility testing of 331 case isolates found only 1 other case of rifampin-resistant disease in Minnesota, USA, during 11 years of statewide surveillance. Point mutations in the RNA polymerase Beta subunit (rpoB) gene were found in isolates from each rifampin-resistant case-patient.
| S-EPMC3367591 | biostudies-literature
Project description:Cytokine stimulated keratinocytes
| PRJNA1076598 | ENA
Project description:Pancreatic beta-cells are essential for survival, being the only cell type capable of insulin secretion. While they are believed to be vulnerable to damage by inflammatory cytokines such as interleukin-1 beta (IL-1beta) and IFN-gamma, we have recently identified physiological roles for cytokine signaling in rodent beta-cells that include that stimulation of antiviral and antimicrobial gene expression and the inhibition of viral replication. In this study, we examine cytokine-stimulated changes in gene expression in human islets using single-cell RNA sequencing. Surprisingly, the global responses of human islets to cytokine exposure were remarkably blunted compared to our previous observations in the mouse. The small population of human islet cells that were cytokine responsive exhibited increased expression of IL-1beta-stimulated antiviral guanylate binding proteins, just like in the mouse. Most human islet cells were not responsive to cytokines, and this lack of responsiveness was associated with high expression of genes encoding ribosomal proteins. We further correlated the expression levels of RPL5 with stress response genes, and when expressed at high levels, RPL5 is predictive of failure to respond to cytokines in all endocrine cells. Further, we postulate that donor cause of death and isolation methodologies may contribute to stress of the islet preparation. Our findings indicate that induction of stress responses in human islets (associated with isolation and/or cause of death) limit cytokine stimulated gene expression, and we urge caution in the evaluation of studies that have examined cytokine-stimulated gene expression in human islets without evaluation of stress-related gene expression.
2024-04-08 | GSE251730 | GEO