Mycobacterium leprae
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PROVIDER: PRJNA328423 | ENA |
REPOSITORIES: ENA
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Project description:Mineralised dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. In this study we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of 16th century human dental calculus from an individual from Trondheim, Norway. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. M. leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual’s dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.
2020-10-19 | PXD017836 | Pride
Project description:To this date, host transcriptome studies in leprosy have focused on Schwann cells, as well as mouse-footpad and skin biopsies. Despite macrophages being the most infected cell types in leprosy lesions, there is no genome-wide experiments with this model. Here, we aimed at identifying host macrophages transcriptional changes induced by live-Mycobacterium leprae infection for 48 hours.
2021-04-16 | GSE162416 | GEO
Project description:Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation –– before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate, and thus likely between the human host and M. leprae bacilli. We found that reQTL are significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, as well as SNPs targeted by recent positive selection. Our study suggests that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.
2017-07-07 | GSE100853 | GEO
Project description:Mycobacterium leprae, the causative agent of leprosy, an obligate intracellular pathogen has the ability to survive and grow for extended periods within phagocytes and Schwann cells. M. leprae genome analysis predicts a highly degraded genome resulting in a significant loss of its genomic coding capacity. Detailed dynamics of carbon sources for energy utilization and growth of M. leprae is unclear. This study, therefore, presents M. leprae transcriptome during in vivo growth and ex vivo stationary phases, and explores metabolic pathways relevant to its growth from global gene expression data. This report provides a glimpse of some of M. leprae nutritional requirements for growth, which most likely, needs to be supplemented, in an axenic growth media.
2022-01-01 | GSE188532 | GEO
Project description:Our object is to characterize the distinguish gene enrichment group in skin of Mycobacterium leprae (M. leprae)-infected footpads compared to that of Mycobacterium leprae (M. leprae) non-infected footpads.
2011-03-17 | GSE24120 | GEO
Project description:Background: Reactions in Leprosy are immune exacerbations that cause debilitating consequences like nerve damage and permanent deformities. Prediction of these reactional states using appropriate biomarkers would enable early treatment interventions to prevent nerve function impairment. The current study investigated whole transcriptomic expression profiles of Mycobacterium leprae (M. leprae) that differentiate leprosy cases in type 2 (Erythema Nodosum Leprosum) reactions with those without reactions in host skin tissue derived RNA. Methods: Post clinical examination, excisional skin biopsy specimens were collected from skin lesions of subjects with and without type 2 reaction. Total RNA was extracted following the Trizol protocol and bacterial RNA was enriched in the samples. A 2 x 400K gene expression array (whole genome tiling array) was designed with the probes having 60-mer oligonucleotides tiling every 10bp of the genome sequence of M. leprae (NC_011896.1). The array comprised 420288 features which include probes and Agilent controls. The quality of RNA was estimated using BioAnalyzer (Agilent Technologies) followed by labelling, reverse transcription, amplification and hybridization to the arrays. The hybridized slides were scanned on a G2600D scanner (Agilent Technologies). The data thus acquired is analysed using GeneSpring GX Version 12.1 software. Data was normalized and fold difference in expression was noted from 359,922 probes which include sense and antisense orientations of 179,961 probes. The differentially expressing M. leprae genomic regions between type 2 reactions and non reactional cases were noted. Results: Considering a statistical cut-off value of 0.6 for fold difference in expression between the test and the control samples, a set of 107 genes indicated statistically significant up-regulation with volcano plot p-values less than 0.05. Functional characterization revealed higher-expression of genes encoding transmembrane proteins (12), regulatory proteins (9), fatty acid biosynthesis (6), amino acid metabolism (13), nucleic acid metabolism (7), DNA replication and repair (7), Secretory proteins (2) Krebs Cycle (1), Glycolysis (1), Drug Efflux Protein (1),Stress Response Protein (1), Energy Metabolism (2), Pantothenate biosynthesis (1), Metalloproteins (3), Hydrolases (1) and Hypothetical Proteins (40). Additionally there are 157 genes that are down regulated in cases with reaction. Conclusion: Differential expression of genes in the human skin biopsy specimens among leprosy cases with type 2 reaction in contrast to those without reaction suggests the role of pathogen associated gene expression triggers with the aetiology of these reactions. As most of the transmembrane and cell wall proteins possess epitope and surface exposed domains, higher expression levels of genes encoding these proteins may have a possible role in enhancing host immune responses characteristic of type 2 reactions in leprosy.
2017-09-01 | GSE85948 | GEO
Project description:Our object is to characterize the distinguish gene enrichment group in skin of Mycobacterium leprae (M. leprae)-infected footpads compared to that of Mycobacterium leprae (M. leprae) non-infected footpads. One-condition experiment, Skin of M. leprae non-infected footpads (control) vs. Skin of M. leprae infected footpads (sample). Biological replicates: 3 control and 3 sample, independently grown and harvested from isolator. One replicate per array.
2011-03-17 | E-GEOD-24120 | biostudies-arrayexpress
Project description:8 leprosy patients including 4 multibacillary (MB) and 4 paucibacillary (PB), and 8 non-leprosy controls including 4 healthy house contacts (HHCs) and 4 endemic controls (ECs) were included in the study. The immune response differences between leprosy patients and controls were evaluated by analyzing the transcriptional profiles of PBMCs to M. leprae sonicate antigens by RNA-seq. The analyses revealed potential biomarkers (including mRNAs and lncRNAs) preferentially expressed in PBMCs in leprosy patients that may be useful for early diagnosis of leprosy.
2021-07-16 | GSE179987 | GEO
Project description:Our goal is to understand the mechanism of granuloma formation in molecular level using Mycobacterium leprae (M. leprae)-infected footpads.
2011-03-17 | GSE22784 | GEO
Project description:Approximately half of M. lepraeâ??s transcriptome consists of inactive gene products. This has an impact on overall energy and resource consumption without potential benefit to this organism. However, multiple translational â??silencingâ?? mechanisms are present, reducing additional energy and resource expenditure required for protein production from these transcripts. The Mycobacterium leprae genome has less than 50% coding capacity and 1,133 pseudogenes. Preliminary evidence suggests that some pseudogenes are expressed. Therefore, defining pseudogene transcriptional and translational potentials should increase our understanding of their impact on M. leprae physiology. To address this, M. leprae was purified from the granulomatous hind footpad tissue of four individual nu/nu nude mice six months post-infection. M. leprae whole genome DNA microarrays representing the 1,614 annotated ORFs and 1,133 identified pseudogenes, were obtained from the Leprosy Research Support and Maintenance of an Armadillo Colony Post-Genome Era, Part I: Leprosy Research Support Contract (NO1 AI-25469) at Colorado State University. To validate 20% of genes positive by microarray analysis, RT-PCR was performed. Results of this study Gene expression analysis identified transcripts from 49% of all M. leprae genes including 57% of all ORFs and 43% of all pseudogenes in the genome. Pseudogenes were randomly distributed throughout the chromosome. Factors resulting in pseudogene transcription included: 1) co-orientation of transcribed pseudogenes with transcribed ORFs within or exclusive of operon-like structures; 2) the paucity of intrinsic stem-loop transcriptional terminators between transcribed ORFs and downstream pseudogenes; and 3) predicted pseudogene promoters. Mechanisms for translational silencing of pseudogene transcripts included the lack of both translational start codons and strong Shine-Dalgarno sequences. Transcribed pseudogenes also contained multiple in-frame stop codons and high Ka/Ks ratios, compared to that of homologs in M. tuberculosis and ORFs in M. leprae. A pseudogene transcript containing an active promoter, strong SD site, a start codon, but containing two in frame stop codons yielded a protein product when expressed in E. coli. Approximately half of M. leprae's transcriptome consists of inactive gene products consuming energy and resources without potential benefit to M. leprae. Presently it is unclear what additional detrimental affect(s) this large number of inactive mRNAs has on the functional capability of this organism. Translation of these pseudogenes may play an important role in overall energy consumption and resultant pathophysiological characteristics of M. leprae. However, this study also demonstrated that multiple translational silencing mechanisms are present, reducing additional energy and resource expenditure required for protein production from the vast majority of these transcripts. The overall design of this study was to identify the transcriptome of M. leprae in the granulomatous tissue of the mouse hind foot pad 6 months post infection.
2010-06-24 | E-GEOD-17191 | biostudies-arrayexpress