Within-patient diversity of Mycobacterium abscessus
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB28875 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR2818440_1.fastq.gz | Fastqsanger.gz | |||
| ERR2818440_2.fastq.gz | Fastqsanger.gz | |||
| ERR2818450_1.fastq.gz | Fastqsanger.gz | |||
| ERR2818450_2.fastq.gz | Fastqsanger.gz |
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Project description:Mycobacterium abscessus is nowadays under the spotlight of the scientific community. This pathogenic mycobacteria is indeed responsible for a wide spectrum of infections involving mostly pulmonary infections in patients with cystic fibrosis. M. abscessus is intrinsically resistant to a broad range of antibiotics, including most antitubercular drugs, and is considered the most pathogenic and chemotherapy-resistant rapidly growing mycobacterium. Consequently, with very limited treatment options, the development of new therapeutic approaches to fight this pathogen are urgently needed. In this context, 19 oxadiazolone (OX) derivatives have been investigated for their antibacterial activity against both the rough (R) and smooth (S) variants of M. abscessus. Several OXs were active against extracellular M. abscessus growth with moderated minimal inhibitory concentrations (MIC), or intracellularly by inhibiting M. abscessus growth inside infected macrophages with MIC values similar to those of imipenem. Such promising results prompted us to identify the potential target enzymes of the sole extra and intracellular inhibitor of M. abscessus growth, i.e., iBpPPOX via activity-based protein profiling combined with mass spectrometry. This approach led to the identification of 21 potential protein candidates being mostly involved in M. abscessus lipid metabolism and/or in cell wall biosynthesis.
2020-08-14 | PXD015680 | Pride
Project description:Non-tuberculous Mycobacteria (NTM) are a group of emerging bacterial pathogens that have been identified in cystic fibrosis (CF) patients with microbial lung infections. The treatment of NTM infection in CF patients is challenging due to the natural resistance of NTM species to many antibiotics. Mycobacterium abscessus (M. abscessus) is one of the most common NTM strains found in the airway of CF patients. In our current study, we characterized the extracellular vesicles (EVs) released by drug-sensitive M. abscessus untreated or treated with clarithromycin, one of the well-known anti-NTM drugs. Our data show that clarithromycin treatment increases mycobacterial protein trafficking into EVs as well as the secretion of EVs in M. abscessus culture. Additionally, EVs released by clarithromycin-treated M. abscessus increase M. abscessus resistance to clarithromycin when compared to EVs from untreated M. abscessus. EV proteomic analysis further indicates that EVs released by clarithromycin-treated M. abscessus carry an increased level of 50S ribosomal subunits, the target of clarithromycin. Taken together, our results suggest that mycobacterial EVs play an important role in increasing M. abscessus resistance to clarithromycin treatment.
2025-05-06 | PXD047862 | Pride
Project description:Mycobacterium abscessus population structure of isolates from Cystic Fibrosis patients
| PRJEB39129 | ENA
Project description:Mycobacterium abscessus (Mabs) is a fast-growing, non-tuberculous mycobacterium responsible for serious lung infections in patients with cystic fibrosis. This bacterium evolves during the pulmonary infection between a smooth (S) and a rough morphotype (R). We have previously isolated the lsr2 gene as being differentially expressed during the transition between Mabs-S and Mabs-R. lsr2 encodes a pleiotropic transcription factor belonging to the superfamily of nucleoid-associated proteins (NAPs), which play an essential role in the hierarchical organization of bacterial chromosomes. The present study aims to unravel the molecular role of Lsr2 in regulating expression of gene involved in the adaptation and the pathobiology of Mabs using both RNA-Seq and ChIP-seq.
2023-11-30 | GSE239869 | GEO
Project description:Mycobacterium abscessus (Mabs) is a fast-growing, non-tuberculous mycobacterium responsible for serious lung infections in patients with cystic fibrosis. This bacterium evolves during the pulmonary infection between a smooth (S) and a rough morphotype (R). We have previously isolated the lsr2 gene as being differentially expressed during the transition between Mabs-S and Mabs-R. lsr2 encodes a pleiotropic transcription factor belonging to the superfamily of nucleoid-associated proteins (NAPs), which play an essential role in the hierarchical organization of bacterial chromosomes. The present study aims to unravel the molecular role of Lsr2 in regulating expression of gene involved in the adaptation and the pathobiology of Mabs using both RNA-Seq and ChIP-seq.
2023-11-30 | GSE239870 | GEO
Project description:Mycobacterium abscessus (Mabs) biofilms are altered in the presence of exogenous heme. We wanted to determine how protein levels were affected by heme. Mabs cells were grown in a modified media formulated to mimic the nutritional environment of the sputum of cystic fibrosis (CF) patients. Mabs cells grown in synthetic CF media (SCFM) typically form submerged biofilms, exogenous heme treatment however prevents this film formation and supports growth of a pellicle at the air-liquid interface. Heme treatment reduced several iron uptake and homeostasis proteins, suggesting heme is acting as an iron source for these bacteria. In addition, multiple proteins were upregulated in heme treatment, however, the function of these proteins remains to be determined.
2025-02-23 | PXD057673 | Pride
Project description:Mycobacterium abscessus is a major human pathogen, mostly infecting people with pre-existing pathological lung conditions such as cystic fibrosis. Only little is known about the ways M. abscessus regulates its virulence factors and pathogenesis phenotypes. The production of glycopeptidolipids (GPL) is a major determinant of virulence of this bacterium, with clinical isolates that lack GPL synthesis and export generally exhibiting more aggressive clinical behavior. The current paradigm is that GPL production is abolished in vivo via irreversible, spontaneous mutations taking place as part of in-host evolution. Little is known about the mechanisms or extent to which GPL production may be regulated. We have found an unusual TetR-like transcription factor of M. abscessus, mab_1638, identified via screening of a comprehensive transposon-mutant library, that appears to be a strong positive regulator of the entire GPL biosynthesis and export gene cluster through a combination of direct and indirect mechanisms. The inactivation of mab_1638 by a transposon led to stable and visually obvious rough colony morphology, as well as increased virulence in infection models, characteristic of rough, non-GPL-producers. Transcriptome analysis found the mab_1638:tn mutant to have 118 differentially expressed genes, including the GPL locus. It appears mab_1638 encodes an unusual TetR transcription factor required for the production of GPL in M. abscessus and therefore having a profound effect on virulence traits. This finding raises the important possibility that M. abscessus strains appearing smooth in laboratory growth conditions may nonetheless downregulate GPL-cluster genes in other conditions and thus acquire the phenotypic characteristics of rough strains.
2025-07-30 | GSE287636 | GEO
Project description:Mycobacterium abscessus is nowadays under the spotlight of the scientific community. This pathogenic mycobacteria is indeed responsible for a wide spectrum of infections involving mostly pulmonary infections in patients with cystic fibrosis. M. abscessus is intrinsically resistant to a broad range of antibiotics, including most antitubercular drugs, and is considered the most pathogenic and chemotherapy-resistant rapidly growing mycobacterium. Consequently, with very limited treatment options, the development of new therapeutic approaches to fight this pathogen are urgently needed. 38 new analogs of Cyclipostins & Cyclophostin (CyC), compounds naturally produced by Streptomyces species, have been synthesized. Their antibacterial activities against clinical isolates belonging to the M. chelonae-abscessus clade, as well as Gram-negative and Gram-positive bacteria have been evaluated by the REMA method. The intracellular activities of the CyC against intramacrophagic M. abscessus have also been investigated and compared to those of imipenem. The CyCs displayed very low toxicity towards host cells and their inhibitory activity was exclusively restricted to mycobacteria. The best candidate, CyC17, showed a high selectivity for mycobacteria with MIC values (<2 up to 40 µg/mL) comparable to those of most classical antibiotics used to treat M. abscessus infections. Of importance, several CyCs were active against extracellular M. abscessus growth (i.e., CyC17 / CyC18β / CyC25 / CyC26) or against intracellular mycobacteria inside macrophages (i.e., CyC7α,β / CyC8α,β) with MIC values similar to or better than those of standard antibiotics. Based on these results, we intended to identify the potential target enzymes of CyC17/CyC26 in M. abscessus by activity-based protein profiling (ABPP) approach coupled with mass spectrometry differential analysis.
2019-10-08 | PXD014255 | Pride
Project description:Mycobacterium abscessus is a major human pathogen, mostly infecting people with pre-existing pathological lung conditions such as cystic fibrosis. Only little is known about the ways M. abscessus regulates its virulence factors and pathogenesis phenotypes. The production of glycopeptidolipids (GPL) is a major determinant of virulence of this bacterium, with clinical isolates that lack GPL synthesis and export generally exhibiting more aggressive clinical behavior. The current paradigm is that GPL production is abolished in vivo via irreversible, spontaneous mutations taking place as part of in-host evolution. Little is known about the mechanisms or extent to which GPL production may be regulated. We have found an unusual TetR-like transcription factor of M. abscessus, mab_1638, identified via screening of a comprehensive transposon-mutant library, that appears to be a strong positive regulator of the entire GPL biosynthesis and export gene cluster through a combination of direct and indirect mechanisms. The inactivation of mab_1638 by a transposon led to stable and visually obvious rough colony morphology, as well as increased virulence in infection models, characteristic of rough, non-GPL-producers. Transcriptome analysis found the mab_1638:tn mutant to have 118 differentially expressed genes, including the GPL locus. It appears mab_1638 encodes an unusual TetR transcription factor required for the production of GPL in M. abscessus and therefore having a profound effect on virulence traits. This finding raises the important possibility that M. abscessus strains appearing smooth in laboratory growth conditions may nonetheless downregulate GPL-cluster genes in other conditions and thus acquire the phenotypic characteristics of rough strains.
2025-07-30 | GSE287715 | GEO
Project description:Mycobacterium abscessus [M. abscessus (sensu lato) or M. abscessus group] comprises three closely related taxa with taxonomic status under revision: M. abscessus sensu stricto, M. bolletii and M. massiliense. We describe here a simple, robust and cost effective PCR-based method for distinguishing among M. abscessus, M. massiliense and bolletii. Based on the M. abscessus ATCC 19977T genome, discriminatory regions were identified between M. abscessus and M. massiliense from array-based comparative genomic hybridization. A typing scheme using PCR primers designed for four of these locations was applied to 46 well-characterized clinical isolates comprising 29 M. abscessus, 15 M. massiliense and 2 M. bolletii previously identified by multi-target sequencing. Interestingly, 2 isolates unequivocally identified as M. massiliense were shown to have a full length erm(41) instead of the expected gene deletion and showed inducible clarithromycin resistance after 14 days. We propose using this PCR-based typing scheme combined with erm(41) PCR for a straightforward identification of M. abscessus, M. massiliense and M. bolletii and assessment of inducible clarithromycin resistance. This method can be easily implemented into a routine workflow providing subspecies level identification within 24 hours of isolation of M. abscessus group. Two-color CGH with 4 independent Mycobacterium clinical isolates and the M massiliense type strain (CCUG 48898) labeled with Cy3 were cohybridized with the M abscessus type strain (ATCC 19977) labeled with Cy5 on a tiling array designed against the M abscessus type strain
2013-07-17 | E-GEOD-43629 | biostudies-arrayexpress