Identification of potential therapeutic targets for Burkholderia cenocepacia by comparative transcriptomics
ABSTRACT:  Transcription profiling of one Burkholderia cenocepacia clinical isolate, J2315, versus a soil isolate, HI2424, in conditions mimicking CF sputum  Transcription profiling of Burkholderia cenocepacia isolates J2315 and HI2424 in media mimicking CF sputum or the soil environment Overall design:  J2315 vs. HI2424 cells in the same condition.  Two-condition experiment. Biological replicates: 4 replicates.
Project description: Transcription profiling of one Burkholderia cenocepacia clinical isolate, J2315, versus a soil isolate, HI2424, in conditions mimicking CF sputum  Transcription profiling of Burkholderia cenocepacia isolates J2315 and HI2424 in media mimicking CF sputum or the soil environment  J2315 vs. HI2424 cells in the same condition.  Two-condition experiment. Biological replicates: 4 replicates.
Project description:Fang2011 - Genome-scale metabolic network of
Burkholderia cenocepacia (iKF1028)
This model is described in the article:
Exploring the metabolic
network of the epidemic pathogen Burkholderia cenocepacia J2315
via genome-scale reconstruction.
Fang K, Zhao H, Sun C, Lam CM, Chang
S, Zhang K, Panda G, Godinho M, Martins dos Santos VA, Wang
BMC Syst Biol 2011; 5: 83
BACKGROUND: Burkholderia cenocepacia is a threatening
nosocomial epidemic pathogen in patients with cystic fibrosis
(CF) or a compromised immune system. Its high level of
antibiotic resistance is an increasing concern in treatments
against its infection. Strain B. cenocepacia J2315 is the most
infectious isolate from CF patients. There is a strong demand
to reconstruct a genome-scale metabolic network of B.
cenocepacia J2315 to systematically analyze its metabolic
capabilities and its virulence traits, and to search for
potential clinical therapy targets. RESULTS: We reconstructed
the genome-scale metabolic network of B. cenocepacia J2315. An
iterative reconstruction process led to the establishment of a
robust model, iKF1028, which accounts for 1,028 genes, 859
internal reactions, and 834 metabolites. The model iKF1028
captures important metabolic capabilities of B. cenocepacia
J2315 with a particular focus on the biosyntheses of key
metabolic virulence factors to assist in understanding the
mechanism of disease infection and identifying potential drug
targets. The model was tested through BIOLOG assays. Based on
the model, the genome annotation of B. cenocepacia J2315 was
refined and 24 genes were properly re-annotated. Gene and
enzyme essentiality were analyzed to provide further insights
into the genome function and architecture. A total of 45
essential enzymes were identified as potential therapeutic
targets. CONCLUSIONS: As the first genome-scale metabolic
network of B. cenocepacia J2315, iKF1028 allows a systematic
study of the metabolic properties of B. cenocepacia and its key
metabolic virulence factors affecting the CF community. The
model can be used as a discovery tool to design novel drugs
against diseases caused by this notorious pathogen.
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Project description:Individual normalized intensity of Burkholderia cenocepacia and Burkholderia seminalis hybridized in a B. cenocepacia array Overall design: A collection of 199 Burkholderia isolates were hybridized against an array targeting five B. cenocepacia strains in order to understand the gene distribution within this species. Burkholderia cenocepacia (n=191) as well as Burkholderia seminalis (n=8, as controls) were used in this analysis.
Project description:Transcriptional profiling of RNA-seq data from two Burkholderia species grown under conditions mimicking the cystic fibrosis lung and the soil environment Overall design: Two condition, two strain experiment. Biological replicates: 2 replicates
Project description:B. cenocepacia is an opportunistic human pathogen that is particularly problematic for patients suffering from cystic fibrosis (CF). In the CF lung, bacteria grow to high densities within the viscous mucus that is limited in oxygen. Pseudomonas aeruginosa, the dominant pathogen in CF patients, is known to grow and survive under oxygen-limited to anaerobic conditions by using micro-oxic respiration, denitrification and fermentative pathways. In contrast, inspection of the genome sequences of available B. cenocepacia strains suggested that B. cenocepacia is an obligate aerobic and non-fermenting bacterium. In accordance with the bioinformatics analysis, we observed that B. cenocepacia H111 is able to grow with as little as 0.1% O2 but not under strictly anoxic conditions. Phenotypic analyses revealed that H111 produced larger amounts of biofilm, pellicle and proteases under micro-oxic conditions (0.5% - 5% O2, i.e. conditions that mimic those encountered in CF lung infection), and was more resistant to several antibiotics. RNA-Seq and shotgun proteomics analyses of cultures of B. cenocepacia H111 grown under micro-oxic and aerobic conditions showed up-regulation of genes involved in the synthesis of the exopolysaccharide (EPS) cepacian as well as several proteases, two isocitrate lyases and other genes potentially important for life in micro-oxia. Oxygen regulation in Burkholderia cenocepacia was investigated using RNA-Seq of cells grown under aerobic or micro-oxic conditions.
Project description:Burkholderia cenocepacia sequence type 32 (ST32) represents one of the most globally distributed strains from Bukrholderia cepacia complex (Bcc), which infected 30% of Czech cystic fibrosis (CF) patients. The aim of this study was to compare gene expression in two pairs of ST32 clinical isolates that were subjected to cultivation in two different conditions, characteristic for chronic B. cenocepacia infection in CF patients. ST32 strain is known to be a problematic epidemic strain, which caused a serious outbreak at the Prague CF centre.
Project description:In this work the genomic expression of two Burkholderia cenocepacia clonal variants (IST439 and IST4113) were compared. These isolates were collected from a chronically colonized cystic-fibrosis patient that has died from the cepacia syndrome. IST439 was the first B. cenocepacia isolate recovered from the patient and it is thought to have initiated the infection while the IST4113 isolate was recovered three years later, after a period of exacerbated infection that compelled the patient to hospitalization and intravenous therapy with gentamicine and ceftazidime. Among other phenotypic differences, IST4113 is much more resistant to a wide range of antimicrobials tested with very different biological targets
Project description:Members of the genus Burkholderia are versatile bacteria capable of colonizing highly diverse environmental niches. In this study, we investigated the global response of the opportunistic pathogen Burkholderia cenocepacia H111 to nitrogen limitation at the transcript and protein expression level. In addition to a classical response to nitrogen starvation, including the activation of glutamine synthetase, PII proteins and the two component regulatory system ntrBC, B. cenocepacia H111 also up-regulated polyhydroxybutyrate (PHB) accumulation and exopolysaccharide (EPS) production in response to nitrogen shortage. A search for consensus sequences in promoter regions of nitrogen responsive genes identified a s54 consensus sequence. The mapping of the s54 regulon as well as the characterization of a s54 mutant suggests an important role of s54 not only in control of nitrogen metabolism, but also in virulence of this organism. Overall design: Nitrogen limitation and s54 regulon in B. cenocepacia