Exploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstruction

Fang, Kechi; Zhao, Hansheng; Sun, Cheng; Lam, Carolyn M.C.; Chang, Suhua; Zhang, Kunlin; Panda, Gurudutta; Godinho, Miguel; Santos, Vítor A. P. Martins dos; Wang, Jing

doi:10.1186/1752-0509-5-83

Cited by 39 publications

(23 citation statements)

References 96 publications

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“…A previously published reconstruction of B. cenocepacia J2315, iKF1028, using the ToBiN reconstruction platform, accounted for 859 reactions, 834 metabolites, and 1,028 genes and was used as a reference for our curation efforts (19). However, we chose to begin with draft reconstructions that were both built using the Model SEED tool (20), currently the most widely used publicly available reconstruction platform, to aid our comparative analyses.…”

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confidence: 99%

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

Bartell¹,

Yen²,

Varga³

et al. 2013

Journal of Bacteriology

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Burkholderia cenocepacia and Burkholderia multivorans are opportunistic drug-resistant pathogens that account for the majority of Burkholderia cepacia complex infections in cystic fibrosis patients and also infect other immunocompromised individuals. While they share similar genetic compositions, B. cenocepacia and B. multivorans exhibit important differences in pathogenesis. We have developed reconciled genome-scale metabolic network reconstructions of B. cenocepacia J2315 and B. multivorans ATCC 17616 in parallel (designated iPY1537 and iJB1411, respectively) to compare metabolic abilities and contextualize genetic differences between species. The reconstructions capture the metabolic functions of the two species and give insight into similarities and differences in their virulence and growth capabilities. The two reconstructions have 1,437 reactions in common, and iPY1537 and iJB1411 have 67 and 36 metabolic reactions unique to each, respectively. After curating the extensive reservoir of metabolic genes in Burkholderia, we identified 6 genes essential to growth that are unique to iPY1513 and 13 genes uniquely essential to iJB1411. The reconstructions were refined and validated by comparing in silico growth predictions to in vitro growth capabilities of B. cenocepacia J2315, B. cenocepacia K56-2, and B. multivorans ATCC 17616 on 104 carbon sources. Overall, we identified functional pathways that indicate B. cenocepacia can produce a wider array of virulence factors compared to B. multivorans, which supports the clinical observation that B. cenocepacia is more virulent than B. multivorans. The reconciled reconstructions provide a framework for generating and testing hypotheses on the metabolic and virulence capabilities of these two related emerging pathogens. Multidrug-resistant pathogens are a severe health concern and can cause chronic infections in a variety of patient populations with limited recourse for treatment. Here, we investigate two multidrug-resistant species, Burkholderia cenocepacia and Burkholderia multivorans, of the Burkholderia cepacia complex (BCC) which are considered dangerous and difficult to treat in patients with cystic fibrosis (CF), chronic granulomatous disease, or compromised immune systems (1). With larger genomes (8.06 Mbp and 7.01 Mbp, respectively) than many other multidrug-resistant pathogens, they also contain an expanded reservoir of genes that may assist their ability to avoid clinical eradication (2-4). Because they are nosocomial, transmissible between patients, and also routinely acquired (and reacquired) from the environment, B. cenocepacia and B. multivorans are the two BCC species most commonly isolated from the sputum of CF patients (5-8). In patients with CF, pulmonary infection with BCC can contribute to the rapid deterioration of lung function known as cepacia syndrome, a necrotizing pneumonia that can lead to bacteremia, septicemia, and increased mortality (9, 10). A combination of high antibiotic resistance and decreased immune function in patients makes B. cen...

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confidence: 99%

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

Bartell¹,

Yen²,

Varga³

et al. 2013

Journal of Bacteriology

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“…In particular, we identified succinyl-CoA:3-ketoacid-coenzyme A transferase subunit B (spots n. 11) involved in the synthesis and degradation of ketone bodies; poly-beta-hydroxybutyrate polymerase (spots n. 12) involved in butanoate metabolism and potentially in rhamnolipid synthesis. The rhamnolipid synthesis is one of the three virulence-associatedpathways in B. cenocepacia J2315 [26]. Although no report demonstrates the synthesis of rhamnolipids in B. cenocepacia, Dubeau et al, emphasized the presence in Burkholderia thailandesis of genes orthologous to those responsible for the synthesis of rhamnolipids in P. aeruginosa [26,27].…”

Section: Cog I Category: Lipid Transport and Metabolismmentioning

confidence: 99%

“…The rhamnolipid synthesis is one of the three virulence-associatedpathways in B. cenocepacia J2315 [26]. Although no report demonstrates the synthesis of rhamnolipids in B. cenocepacia, Dubeau et al, emphasized the presence in Burkholderia thailandesis of genes orthologous to those responsible for the synthesis of rhamnolipids in P. aeruginosa [26,27]. We also identified a putative oxidoreductase (spot n. 13) and the 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, IspG (spot n. 14) involved in biosynthesis of isoprenoids.…”

Section: Cog I Category: Lipid Transport and Metabolismmentioning

confidence: 99%

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RND-4 efflux transporter gene deletion in Burkholderia cenocepacia J2315: a proteomic analysis

Gamberi

Rocchiccioli²,

Papaleo³

et al. 2013

J Proteome Sci Comput Biol

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Background: The Burkholderia cenocepacia J2315 is Gram-negative bacterium that is a pathogen for cystic fibrosis (CF) patients. It displays a high-level of resistance to most antimicrobial drugs. In Gram-negative bacteria, the ResistanceNodulation-Cell Division (RND) transporter family has a poorly understood role in multidrug resistance. In a previous publication we analysed the RND-4 and RND-9 transporters by microarray analysis. The obtained results suggested that only RND-4 contributes to the antibiotic resistance. The aim of this study was to investigate the role of this efflux transporter from a proteomic point of view.

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“…The BCC comprises at least 17 closely related species of the β-proteobacteria, which have developed diverse niches from a natural environment to humans (Fang et al 2011;Sousa et al 2011). Burkholderia cenocepacia is one of the two most common pathogens to cause infection (sometimes death effects) on patients with CF, accounting for 50 % to 80 % of the infection cases .…”

Section: Introductionmentioning

confidence: 99%

Analysis of genomic characters reveals that four distinct gene clusters are correlated with different functions in Burkholderia cenocepacia AU 1054

Yuan

Yang

Ren

et al. 2013

Appl Microbiol Biotechnol

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Possessing three circular chromosomes is a distinct genomic characteristic of Burkholderia cenocepacia AU 1054, a clinically important pathogen in cystic fibrosis. In this study, base composition, codon usage and functional role category were analyzed in the B. cenocepacia AU 1054 genome. Although no bias in the base and codon usage was detected between any two chromosomes, function differences did exist in the genes of each chromosome. Similar base composition and differential functional role categories indicated that genes on these three chromosomes were relatively stable and that a proper division of labor was established. Based on variations in the base or codon usage, four small gene clusters were observed in all of the genes. Multivariate analysis revealed that protein hydrophobicity played a predominant role in shaping base usage bias, while horizontal gene transfer and the gene expression level were the two most important factors that affected the codon usage bias. Interestingly, we also found that these gene clusters were correlated with different biological functions: (i) 45 pyrimidine-leadingcodon preferred genes were predominantly involved in regulatory function; (ii) most drug resistance-related genes involved in 826 genes that coding for hydrophobic proteins; (iii) most of the 111 horizontal transfer genes were responsible for genomic plasticity; and (iv) 73 highly expressed genes (predicted by their codon adaptation index values) showed environmental adaptation to cystic fibrosis. Our results showed that genes with base or codon usage bias were affected by mutational pressure and natural selection, and their functions could contribute to drug assistance and transmissible activity in B. cenocepacia.

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Exploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstruction

Cited by 39 publications

References 96 publications

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

Comparative Metabolic Systems Analysis of Pathogenic Burkholderia

RND-4 efflux transporter gene deletion in Burkholderia cenocepacia J2315: a proteomic analysis

Analysis of genomic characters reveals that four distinct gene clusters are correlated with different functions in Burkholderia cenocepacia AU 1054

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