Beijing sublineages pathogenicity
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR538422_1.fastq.gz | Fastqsanger.gz | |||
| ERR538422_2.fastq.gz | Fastqsanger.gz | |||
| ERR538423_1.fastq.gz | Fastqsanger.gz | |||
| ERR538423_2.fastq.gz | Fastqsanger.gz | |||
| ERR538424_1.fastq.gz | Fastqsanger.gz |
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Project description:Autophagy is a conserved lysosomal-dependent cellular degradation process shown to play a key role in immune defense against Mycobacterium tuberculosis inside host macrophages. Induction of autophagy enhances mycobacterial phagosome acquisition of lysosomal hydrolases, resulting in the destruction of intracellular M. tuberculosis reference strain H37Rv and strains belonging to the East African Indian genotype. However, our previous study showed that strains belonging to the hypervirulent M. tuberculosis Beijing genotype have a special ability to resist autophagic killing but the mechanism involved remains unclear. In this study, we carried out whole transcriptome analyses of host macrophages infected with the autophagy resistant Beijing strain compared to that of H37Rv. Our results identified several genes that are differentially regulated in the Beijing strain-infected host cells including those function in the lysosome positioning pathway. Host macrophages depleted of Kxd1 and Pleckhm2, two proteins in this pathway, can now enhance the lysosomal hydrolase acquisition into the Beijing phagosomes and restrict the bacterial survival upon autophagy induction. High-content image analysis showed an increase in lysosome numbers at the cell periphery in host cells infected with the autophagy resistant Beijing strain in a Pleckhm2-dependent manner. Taken together, these data indicated that the M. tuberculosis Beijing strain escapes autophagic elimination by upregulating the lysosome positioning pathway resulting in an increase in lysosome relocation toward the cell periphery and therefore sparing the mycobacteria from autophagic restriction. Our work thus identified new strategy employed by M. tuberculosis to evade autophagy which may provide potential new targets for drug discovery against tuberculosis
2021-03-02 | GSE151633 | GEO
Project description:In this study we developed a guinea pig oligonucleotide microarray (GPOM) comprising of a total number of 45,220 features including 43,803 valid features from different mammalian species. These features are inclusive of 2971 newly annotated probes corresponding to 344 unique genes of guinea pig. As a case study, we utilized this array to examine the gene expression profile in guinea pig lungs in response to infection with Mycobacterium tuberculosis. Studying the global gene expression profile in guinea pigs allowed identification of the disease signature of pulmonary TB infection represented by several unique genes that are differentially regulated in this model. While, 1344 unique genes exhibited marked up regulation, 1856 genes were significantly down regulated. The newly developed tool not only finds its utility in studying the global gene expression profile associated with vaccination and/or M. tuberculosis infection in this highly useful animal model but would also be immensely useful in identification of new drug targets, testing of therapies, molecular genetic analysis for diseases other than tuberculosis as well. Genotypic Technology designed Custom Cavia porcellus 4x44k Gene Expression Array (Agilent-AMADID-019424) * In order to validate the GPOM developed in this study, we compared the gene expression profile of guinea pig lungs at 10 weeks post- M. tuberculosis infection with respect to that obtained from normal uninfected animals. To address this, guinea pigs were aerosol infected with M. tuberculosis, lungs were harvested at 10 weeks post-infection and RNA obtained from infected lungs was employed for cDNA synthesis and microarray hybridization. The gene expression was compared with the RNA sample obtained from the lungs of normal uninfected guinea pigs.
2012-10-01 | E-GEOD-32447 | biostudies-arrayexpress
Project description:Transcriptional profile comparison among Beijing and non-Beijing M. tuberculosis isolates.
2016-06-24 | GSE83677 | GEO
Project description:Background. The Beijing family of Mycobacterium tuberculosis is dominant in countries in East Asia. Genomic polymorphisms are a source of diversity within the M.tuberculosis genome and may account for the variation of virulence among M.tuberculosis isolates. To date there are no studies that have examined the genomic composition of M.tuberculosis isolates from the high TB-burden country, Myanmar. Methodology/Principle findings. Twenty-two M.tuberculosis isolates from Myanmar were screened on whole-genome arrays containing genes from M.tuberculosis H37Rv, M.tuberculosis CDC1551 and M.bovis AF22197. Screening identified 198 deletions or extra regions in the clinical isolates compared to H37Rv. Twenty-two regions differentiated between Beijing and non-Beijing isolates and were verified by PCR on an additional 40 isolates. Six regions (Rv0071-0074 [RD105], Rv1572-1576c [RD149], Rv1585c-1587c[RD149], MT1798-Rv1755c [RD152], Rv1761c [RD152] and Rv0279c) were deleted in Beijing isolates, of which 4 (Rv1572-1576c, Rv1585c-1587c, MT1798-Rv1755c and Rv1761c) were variably deleted among ST42 isolates, indicating a closer relationship between the Beijing and ST42 lineages. The TbD1 region, Mb1582-Mb1583 was deleted in Beijing and ST42 isolates. One M.bovis gene of unknown function, Mb3184c was present in all isolates, except 11 of 13 ST42 isolates. The CDC1551 gene, MT1360 coding for a putative adenylate cyclase, was present in all Beijing and ST42 isolates (except 1). The pks15/1 gene, coding for a putative virulence factor, was intact in all Beijing and non-Beijing isolates, except in ST42 and ST53 isolates. Conclusion. This study describes previously unreported deletions/extra regions in Beijing and non-Beijing M.tuberculosis isolates. The modern and highly frequent ST42 lineage showed a closer relationship to the hypervirulent Beijing lineage than to the ancient non-Beijing lineages. The pks15/1 gene was disrupted only in modern non-Beijing isolates. This is the first report of an in-depth analysis on the genomic diversity of M.tuberculosis isolates from Myanmar. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-66
2008-09-26 | E-BUGS-66 | biostudies-arrayexpress
Project description:In this study we developed a guinea pig oligonucleotide microarray (GPOM) comprising of a total number of 45,220 features including 43,803 valid features from different mammalian species. These features are inclusive of 2971 newly annotated probes corresponding to 344 unique genes of guinea pig. As a case study, we utilized this array to examine the gene expression profile in guinea pig lungs in response to infection with Mycobacterium tuberculosis. Studying the global gene expression profile in guinea pigs allowed identification of the disease signature of pulmonary TB infection represented by several unique genes that are differentially regulated in this model. While, 1344 unique genes exhibited marked up regulation, 1856 genes were significantly down regulated. The newly developed tool not only finds its utility in studying the global gene expression profile associated with vaccination and/or M. tuberculosis infection in this highly useful animal model but would also be immensely useful in identification of new drug targets, testing of therapies, molecular genetic analysis for diseases other than tuberculosis as well.
2012-10-01 | GSE32447 | GEO
Project description:Mycobacterium tuberculosis str. Beijing/NITR203 Genome sequencing
| PRJNA193385 | ENA
Project description:mycobacterium tuberculosis strain:Beijing lineage Genome sequencing
| PRJNA273899 | ENA
Project description:Transcriptional profile comparison among Beijing and non-Beijing M. tuberculosis isolates. Three M. tuberculosis strains were compared. The laboratory reference strain, H37Rv, belongs to the Euro-American or lineage 4. Two clinical isolates of the East-Asian or lineage 2: 98_1663 is a pre-Beijing or Group 1 isolate, and HN878 is a Beijing or Group 5 isolate. Three replicates were performed for each comparison using two different biological samples.
2016-06-24 | E-GEOD-83677 | biostudies-arrayexpress
Project description:Tuberculosis continues as an important public health problem. Particularly considering Beijing-family strains of Mycobacterium tuberculosis, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several over-expressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Contrary, mice infected with BL displayed a profile which included the over-expression of several genes associated with immune- suppression, including Nkiras, Dleu2 and Sphk2, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis.
2021-03-25 | GSE169541 | GEO
Project description:Mycobacterium tuberculosis strain:Beijing lineage Raw sequence reads
| PRJNA725394 | ENA