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Article 2021 · 8 atıf

Revealing the Metabolic Alterations during Biofilm Development of <i>Burkholderia cenocepacia</i> Based on Genome-Scale Metabolic Modeling

Altay, Ozlem, Zhang, Cheng, Turkez, Hasan, Nielsen, Jens, Uhlen, Mathias, Mardinoglu, Adil

Özet

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.

Anahtar Kelimeler
Burkholderia cenocepacia biofilm genome-scale metabolic models synthetic lethality transcriptomics omics integration BIOSYNTHESIS GROWTH TARGET
WoS Kategorileri
Biochemistry & Molecular Biology
Sürdürülebilir Kalkınma Amaçları
Künye
Dergi
METABOLITES
Yıl
2021
Cilt
11
Sayı
4
eISSN
2218-1989
DOI
10.3390/metabo11040221
WoS UID
WOS:000643271500001
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