Revealing the Metabolic Alterations during Biofilm Development of Burkholderia cenocepacia Based on Genome-Scale Metabolic Modeling.
Ozlem AltayCheng ZhangHasan TurkezJens NielsenMathias UhlenAdil MardingluPublished in: Metabolites (2021)
Burkholderia cenocepacia 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 B. cenocepacia. 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.
Keyphrases
- pseudomonas aeruginosa
- staphylococcus aureus
- cystic fibrosis
- candida albicans
- biofilm formation
- single cell
- end stage renal disease
- induced apoptosis
- amino acid
- electronic health record
- escherichia coli
- high throughput
- big data
- genome wide
- ejection fraction
- newly diagnosed
- prognostic factors
- transcription factor
- lung function
- oxidative stress
- peritoneal dialysis
- dna methylation
- data analysis
- drug induced
- signaling pathway
- climate change
- chronic obstructive pulmonary disease