Revealing the metabolic alterations during biofilm development of burkholderia cenocepacia based on genome-scale metabolic modeling

TY - JOUR

T1 - Revealing the metabolic alterations during biofilm development of burkholderia cenocepacia based on genome-scale metabolic modeling

AU - Altay, Ozlem

AU - Zhang, Cheng

AU - Turkez, Hasan

AU - Nielsen, Jens

AU - Uhlén, Mathias

AU - Mardinoglu, Adil

N1 - Funding Information: Funding: This research was funded by Knut and Alice Wallenberg Foundation. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

KW - Biofilm

KW - Burkholderia cenocepacia

KW - Genome-scale metabolic models

KW - Omics integration

KW - Synthetic lethality

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85104358358&partnerID=8YFLogxK

U2 - 10.3390/metabo11040221

DO - 10.3390/metabo11040221

M3 - Article

AN - SCOPUS:85104358358

SN - 2218-1989

VL - 11

JO - Metabolites

JF - Metabolites

IS - 4

M1 - 221

ER -