Dataset Information

Ample glycosylation in membrane and cell envelope protein explains phenotypic diversity, virulence and AMR in the Mycobacterium tuberculosis complex

ABSTRACT: Glycoproteomics is likely to identify Mtb virulence factors because glycoproteins on the bacterial cell envelope are used by mycobacteria to enter the primary human host cell, the macrophage. It has been proposed that Mtb interacts with mannose receptors on host cells via mannosylated proteins to enter the macrophages. Despite the vital importance of these proteins in Mtb pathogenesis, our current knowledge of Mtb glycoproteins is still limited, and only a few secreted and cell wall-associated glycoproteins have to date been described. Previous studies have used laboratory strains as model systems to study glycosylation in Mtb. However, only a few sub-groups within the genetically conserved MTBC appear to cause extensive outbreaks with different clinical presentation and AMR. In this study, we employed qualitative and quantitative mass spectrometry and bioinformatics to explore the glycoproteomic patterns of clinical isolates from four lineages of the MTBC, lineages 3, 4, 5 and 7, to investigate the role of protein glycosylation in Mtb adaptation, survival and AMR.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mycobacterium Tuberculosis H37rv

SUBMITTER: Alemayehu Godana Birhanu

LAB HEAD: Alemayehu Godana Birhanu

PROVIDER: PXD009676 | Pride | 2019-03-25

REPOSITORIES: Pride

ACCESS DATA

Publications

Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.

Birhanu Alemayehu Godana AG Yimer Solomon Abebe SA Kalayou Shewit S Riaz Tahira T Zegeye Ephrem Debebe ED Holm-Hansen Carol C Norheim Gunnstein G Aseffa Abraham A Abebe Markos M Tønjum Tone T

Scientific reports 20190227 1

Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb). PTMs such as glycosylation play a significant role in Mtb adaptive processes. The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry. A total of 2944 glycosylation events were discovered in 1325 proteins. ...[more]

PMID: 30814666

Similar Datasets

Project description:The presence of Donor-Specific anti-HLA Antibodies (DSA) is associated with an increased risk of both acute and chronic antibody-mediated rejection (AMR) in kidney allografts. AMR has remained challenging in kidney transplantation and is the major cause of late allograft loss. However, not all patients with DSA develop AMR, leading to the question of whether this represents accommodation, if other protective mechanisms exist or if this is actually a state of pre-rejection. Clinical and histological features, and gene expression profiles of kidney biopsy and blood samples of donor-specific antibody (DSA)+ patients without rejection were compared to antibody-mediated rejection (AMR) patients to elucidate the mechanisms involved in prevention of AMR. Of the 71 DSA+ patients, 46 had diagnosis of AMR and 25 did not show rejection. 50 DSA- patients without rejection were used as control. A subgroup of patients with available biopsy (n=61) and blood samples (n=54) were analyzed by microarrays. Both, DSA+/AMR+ and DSA+/AMR- biopsies showed increased expression of gene transcripts associated with cytotoxic T, natural killer cells, macrophages, interferon-gamma and rejection compared to DSA- biopsies. Regulatory T cell transcripts were up-regulated in DSA+/AMR+ and B cell transcripts in DSA+/AMR- biopsies. Whole blood gene expression analysis showed increased immune activity in only DSA+/AMR+ patients. There were no differentially expressed tolerant genes studied (n=14) in the blood or biopsy specimens of DSA+/AMR- patients. During a median 36 months follow-up, 4 DSA+/AMR- patients developed AMR, 12 continued to have DSAs but 9 lost DSAs. Gene expression profiles did not predict the development of AMR or persistence of DSAs. These results indicate increased immune activity in DSA+/AMR- biopsies despite lack of histologic findings of rejection. All clinically indicated kidney transplant biopsies performed at our institution after January 2009 were reviewed and 263 patients with anti-HLA antibody testing at the time of biopsy were identified. There were 71 DSA+ and 192 DSA- patients (Figure 1). Of the 71 DSA+ patients, 46 had biopsy diagnosis of acute AMR (n=9) or chronic AMR (n=37), and 25 had normal histopathology or minimal non-specific interstitial fibrosis/tubular atrophy (IFTA). Of the 192 DSA- patients, 50 patients with normal histology and/or mild non-specific IFTA were used as a control group. Clinical and histopathological findings of these 3 groups (DSA+/AMR+, DSA+/AMR- and DSA-) were analyzed. A subgroup of patients who were enrolled in the Institutional Review Board-approved âImmune Monitoring Studyâ who had clinically indicated biopsy (n=61) and whole blood samples (n=54) stored were used for genomic analysis. Twenty-eight biopsy and blood samples from DSA+/AMR+ patients, 13 biopsy and 14 blood samples from DSA+/AMR- patients, and 20 biopsy and 12 blood samples from DSA- patients, were available for microarray analysis.

Dataset Information

Ample glycosylation in membrane and cell envelope protein explains phenotypic diversity, virulence and AMR in the Mycobacterium tuberculosis complex

Publications

Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure