Granulibacter bethesdensis CGDNIH1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA17111 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human bacterial pathogen that infects Chronic Granuloma Disease patients
| PRJNA68647 | ENA
Project description:Human bacterial pathogen that infects Chronic Granuloma Disease patients
| PRJNA68629 | ENA
Project description:Genome sequencing of human bacterial pathogen that infects Chronic Granuloma Disease patients
| PRJNA68649 | ENA
Project description:Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by CGD PMN and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in normal and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of anti-apoptotic genes (e.g., XIAP, GADD45B) and downregulation of pro-apoptotic genes (e.g., CASP8, APAF1) in infected PMN. Transcript and protein levels of inflammation and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered expression of ROS-resistance genes in the presence of normal but not CGD PMN. Bacterial stress response genes, including ClpB, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knock down demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included upregulation of pyruvate dehydrogenase. Pharmacologic inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis by Granulibacter in cells from permissive (CGD) and non-permissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen.
2015-09-08 | GSE55849 | GEO
Project description:Chronic granulomatous disease (CGD) is a rare genetic defect in neutrophil superoxide formation in which patients develop recurrent life-threatening infections with Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, Nocardia and Aspergillus species. We recently described a novel member of the Acetobacteraceae, Granulibacter bethesdensis, in several CGD patients who presented with fever and lymphadenitis. In order to more fully understand the infectivity of this novel human pathogen we sequenced the genome of Granulibacter bethesdensis to its entirety and identified a single, circular chromosome consisting of 2,708,355 base pairs with a G+C content of 59.07%. We identified 2,437 predicted protein-encoding open reading frames (ORFS) of which, 75.17% have a biological functional annotation. Comparison of G. bethesdensis to another member of the Acetobacteraceae, Gluconobacter oxydans, indicates functional conservation between the two genomes, but also the presence of ORFS unique to G. bethesdensis consistent with virulence, adherence, DNA uptake and methanol utilization. In addition, comparative genome analysis of G. bethesdensis to known CGD pathogens demonstrated broad conservation of putative virulence factors. Finally, G. bethesdensis isolate DNAs were hybridized to a high density custom array, towards characterizing plasticity zones, which occur in regions with genes related to DNA uptake systems, transcriptional regulators and those of unknown function. Together these results provide insight into a novel human pathogen, which is geographically dispersed, is undergoing gain or loss of important DNA elements and which infects patients with CGD.
2007-11-23 | E-TABM-148 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3294967 | biostudies-literature
Project description:Simultaneous Host-Pathogen transcriptome analysis during Granulibacter bethesdensis infection of normal and chronic granulomatous disease neutrophils
| PRJNA241134 | ENA
Project description: Not available
| S-EPMC5442635 | biostudies-literature
Project description:Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by CGD PMN and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in normal and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of anti-apoptotic genes (e.g., XIAP, GADD45B) and downregulation of pro-apoptotic genes (e.g., CASP8, APAF1) in infected PMN. Transcript and protein levels of inflammation and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered expression of ROS-resistance genes in the presence of normal but not CGD PMN. Bacterial stress response genes, including ClpB, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knock down demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included upregulation of pyruvate dehydrogenase. Pharmacologic inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis by Granulibacter in cells from permissive (CGD) and non-permissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen. pathogen time series 0-1-4-24 in CGD subjects and normals : host time series 0-1-4-24 in CGD subjects and normals non-infected and infected with Gb
2015-09-08 | E-GEOD-55849 | biostudies-arrayexpress
Project description:Granulibacter bethesdensis overview
| PRJNA35915 | ENA