MiRNA profile of THP-1 macrophage infected with different MTB strains
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65811 | GEO | 2015/07/01
SECONDARY ACCESSION(S): PRJNA275119
REPOSITORIES: GEO
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Project description:We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of (1) Beijing/W and non-Beijing/W clinical strains, and (2) susceptible and multidrug-resistant (MDR-) MTB strains. THP-1 cells were induced differentiation into a macrophage phenotype. Then cells were infected with three MDR (INHR, RIFR) Beijing/W, three sensitive (INHS, RIFS) Beijing/W, three MDR(INHR, RIFR) non-Beijing/W, and three sensitive (INHS, RIFS) non-Beijing/W strains. Total RNA were extracted and transfered into cDNA for miRNA profile analysis. Non-infected cells were used as control.
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2018-12-26 | GSE115495 | GEO
Project description:The W-Beijing family of Mycobacterium tuberculosis (Mtb) strains is known for its high-prevalence and -virulence, as well as for its genetic diversity, as recently reported by our laboratories and others. However, little is known about how the immune system responds to these strains. To explore this issue, here we used reverse engineering and genome-wide expression profiling of human macrophage-like THP-1 cells infected by different Mtb strains of the W-Beijing family, as well as by the reference laboratory strain H37Rv. Detailed data mining revealed that host cell transcriptome responses to H37Rv and to different strains of the W-Beijing family are similar and overwhelmingly induced during Mtb infections, collectively typifying a robust gene expression signature ("THP1r2Mtb-induced signature"). Analysis of the putative transcription factor binding sites in promoter regions of genes in this signature identified several key regulators, namely STATs, IRF-1, IRF-7, and Oct-1, commonly involved in interferon-related immune responses. The THP1r2Mtb-induced signature appeared to be highly relevant to the interferon-inducible signature recently reported in active pulmonary tuberculosis patients, as revealed by cross-signature and cross-module comparisons. Further analysis of the publicly available transcriptome data from human patients showed that the signature appears to be relevant to active pulmonary tuberculosis patients and their clinical therapy, and be tuberculosis specific. Thus, our results provide an additional layer of information at the transcriptome level on mechanisms involved in host macrophage response to Mtb, which may also implicate the robustness of the cellular defense system that can effectively fight against genetic heterogeneity in this pathogen.
2011-12-01 | GSE29628 | GEO
Project description:The identification of multidrug resistant (MDR), extensively and totally drug resistant Mycobacterium tuberculosis (Mtb), in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS) compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS) at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S) microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB), cell wall biosynthesis (emb genes), protein synthesis (rpl) and additional central metabolic pathways (ppdK, pknH, pfkB) were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB) in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with least fitness cost. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-134]
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Project description:Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) strains and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence data. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB (HR-MTB), 7 were resistant only to one antibiotic (3 were resistant only to ethambutol and 3 isolate to streptomycin while one isolate showed resistance to fluoroquinolones), 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB (pre-XDR). This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of TB infection.
2023-11-17 | E-MTAB-13058 | biostudies-arrayexpress
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Project description:Septoria leaf blotch is a worldwide threat for wheat and mainly controlled by the application of synthetic fungicides. The fungal pathogen responsible for this disease, Zymoseptoria tritici, was shown as highly adaptable to its host plant, but also to fungicide challenge. Over the past decades it developed resistance to most fungicides due to target site modifications. Recently isolated strains showed cross-resistance to diverse fungicides and to unrelated drugs, suggesting a resistance mechanism that seems rarer in phytopathogenic fungi, known as multidrug resistance (MDR) in other organisms. In this study we show for two Z. tritici MDR strains, MDR6 and MDR7, enhanced prochloraz efflux sensitive to the modulators amitryptiline and chlorpromazine. Efflux was also inhibited by verapamil in the MDR7strain. Transcriptomics revealed several overexpressed transporter genes in both MDR strains, out of which the expression of the MgMFS1 transporter gene was the strongest and constitutively high in tested MDR field strains. Its inactivation in the MDR6 strain abolished resistance to fungicides with different modes of action revealing its involvement in the MDR phenomenon in Z. tritici.
2015-06-10 | GSE58672 | GEO
Project description:Septoria leaf blotch is a worldwide threat for wheat and mainly controlled by the application of synthetic fungicides. The fungal pathogen responsible for this disease, Zymoseptoria tritici, was shown as highly adaptable to its host plant, but also to fungicide challenge. Over the past decades it developed resistance to most fungicides due to target site modifications. Recently isolated strains showed cross-resistance to diverse fungicides and to unrelated drugs, suggesting a resistance mechanism that seems rarer in phytopathogenic fungi, known as multidrug resistance (MDR) in other organisms. In this study we show for two Z. tritici MDR strains, MDR6 and MDR7, enhanced prochloraz efflux sensitive to the modulators amitryptiline and chlorpromazine. Efflux was also inhibited by verapamil in the MDR7strain. Transcriptomics revealed several overexpressed transporter genes in both MDR strains, out of which the expression of the MgMFS1 transporter gene was the strongest and constitutively high in tested MDR field strains. Its inactivation in the MDR6 strain abolished resistance to fungicides with different modes of action revealing its involvement in the MDR phenomenon in Z. tritici. A total of four strains were compared, two sensitive (IPO323, S6) and two MDR strains (09-ASA-3apz; 09-CB01) with three replicates each. All strains were grown in liquid YPD medium to exponential growth.
2015-06-10 | E-GEOD-58672 | biostudies-arrayexpress