Granulibacter bethesdensis
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ABSTRACT:
PROVIDER: PRJNA35915 | ENA |
REPOSITORIES: ENA
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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: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:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA347349 | ENA
Project description:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA347348 | ENA
Project description:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA352786 | ENA
Project description:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA352742 | ENA
Project description:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA347332 | ENA
Project description:Comparative genomic and phenotypic analysis of Granulibacter bethesdensis
| PRJNA347345 | ENA
Project description:Chronic granulomatous disease (CGD) is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patients with CGD from North and Central America. Genomic typing showed that 3 patients had recurrent infection months to years after apparent clinical cure. Two patients were infected with the same strain as previously isolated, and 1 was infected with a genetically distinct strain. This organism is multidrug resistant, and therapy required surgery and combination antimicrobial drugs, including long-term ceftriaxone. G. bethesdensis causes necrotizing lymphadenitis in CGD, which may recur or relapse.
| S-EPMC3294967 | biostudies-literature