Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling
<i>Burkholderia cenocepacia</i> is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the...
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MDPI AG
2021-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/4/221 |
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| author | Ozlem Altay Cheng Zhang Hasan Turkez Jens Nielsen Mathias Uhlén Adil Mardinoglu |
| author_facet | Ozlem Altay Cheng Zhang Hasan Turkez Jens Nielsen Mathias Uhlén Adil Mardinoglu |
| author_sort | Ozlem Altay |
| collection | DOAJ |
| description | <i>Burkholderia cenocepacia</i> is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of <i>B. cenocepacia</i>. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases. |
| first_indexed | 2024-03-10T12:35:41Z |
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| id | doaj.art-5c53fff984e347c08f1b3fba7de682b0 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T12:35:41Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-5c53fff984e347c08f1b3fba7de682b02023-11-21T14:17:12ZengMDPI AGMetabolites2218-19892021-04-0111422110.3390/metabo11040221Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic ModelingOzlem Altay0Cheng Zhang1Hasan Turkez2Jens Nielsen3Mathias Uhlén4Adil Mardinoglu5Science for Life Laboratory, KTH–Royal Institute of Technology, 171 65 Solna, SwedenScience for Life Laboratory, KTH–Royal Institute of Technology, 171 65 Solna, SwedenDepartment of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum 25 240, TurkeyDepartment of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, SwedenScience for Life Laboratory, KTH–Royal Institute of Technology, 171 65 Solna, SwedenScience for Life Laboratory, KTH–Royal Institute of Technology, 171 65 Solna, Sweden<i>Burkholderia cenocepacia</i> is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of <i>B. cenocepacia</i>. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases.https://www.mdpi.com/2218-1989/11/4/221<i>Burkholderia cenocepacia</i>biofilmgenome-scale metabolic modelssynthetic lethalitytranscriptomicsomics integration |
| spellingShingle | Ozlem Altay Cheng Zhang Hasan Turkez Jens Nielsen Mathias Uhlén Adil Mardinoglu Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling Metabolites <i>Burkholderia cenocepacia</i> biofilm genome-scale metabolic models synthetic lethality transcriptomics omics integration |
| title | Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling |
| title_full | Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling |
| title_fullStr | Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling |
| title_full_unstemmed | Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling |
| title_short | Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling |
| title_sort | revealing the metabolic alterations during biofilm development of i burkholderia cenocepacia i based on genome scale metabolic modeling |
| topic | <i>Burkholderia cenocepacia</i> biofilm genome-scale metabolic models synthetic lethality transcriptomics omics integration |
| url | https://www.mdpi.com/2218-1989/11/4/221 |
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