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

2.50
Hdl Handle:
http://hdl.handle.net/10033/620683
Title:
Exploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstruction
Authors:
Fang, Kechi; Zhao, Hansheng; Sun, Changyue; Lam, Carolyn M C; Chang, Suhua; Zhang, Kunlin; Panda, Gurudutta; Godinho, Miguel; Martins dos Santos, Vítor A P; Wang, Jing
Abstract:
Abstract 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.
Citation:
BMC Systems Biology. 2011 May 25;5(1):83
Issue Date:
25-May-2011
URI:
http://dx.doi.org/10.1186/1752-0509-5-83; http://hdl.handle.net/10033/620683
Type:
Journal Article
Appears in Collections:
Publications of the RG Systems and synthetic biology (SSBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorFang, Kechien
dc.contributor.authorZhao, Hanshengen
dc.contributor.authorSun, Changyueen
dc.contributor.authorLam, Carolyn M Cen
dc.contributor.authorChang, Suhuaen
dc.contributor.authorZhang, Kunlinen
dc.contributor.authorPanda, Guruduttaen
dc.contributor.authorGodinho, Miguelen
dc.contributor.authorMartins dos Santos, Vítor A Pen
dc.contributor.authorWang, Jingen
dc.date.accessioned2017-01-06T10:24:53Z-
dc.date.available2017-01-06T10:24:53Z-
dc.date.issued2011-05-25en
dc.identifier.citationBMC Systems Biology. 2011 May 25;5(1):83en
dc.identifier.urihttp://dx.doi.org/10.1186/1752-0509-5-83en
dc.identifier.urihttp://hdl.handle.net/10033/620683-
dc.description.abstractAbstract 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.en
dc.titleExploring the metabolic network of the epidemic pathogen Burkholderia cenocepacia J2315 via genome-scale reconstructionen
dc.typeJournal Articleen
dc.language.rfc3066enen
dc.rights.holderFang et al; licensee BioMed Central Ltd.en
dc.date.updated2015-09-04T08:24:26Zen
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