Genome-Scale Metabolic Modeling Reveals Metabolic Alterations of Multidrug-Resistant Acinetobacter baumannii in a Murine Bloodstream Infection Model

Microorganisms
Jinxin ZhaoJian Li

Abstract

Multidrug-resistant (MDR) Acinetobacter baumannii is a critical threat to human health globally. We constructed a genome-scale metabolic model iAB5075 for the hypervirulent, MDR A. baumannii strain AB5075. Predictions of nutrient utilization and gene essentiality were validated using Biolog assay and a transposon mutant library. In vivo transcriptomics data were integrated with iAB5075 to elucidate bacterial metabolic responses to the host environment. iAB5075 contains 1530 metabolites, 2229 reactions, and 1015 genes, and demonstrated high accuracies in predicting nutrient utilization and gene essentiality. At 4 h post-infection, a total of 146 metabolic fluxes were increased and 52 were decreased compared to 2 h post-infection; these included enhanced fluxes through peptidoglycan and lipopolysaccharide biosynthesis, tricarboxylic cycle, gluconeogenesis, nucleotide and fatty acid biosynthesis, and altered fluxes in amino acid metabolism. These flux changes indicate that the induced central metabolism, energy production, and cell membrane biogenesis played key roles in establishing and enhancing A. baumannii bloodstream infection. This study is the first to employ genome-scale metabolic modeling to investigate A. baumannii infec...Continue Reading

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Datasets Mentioned

BETA
AB5075
SRS7522398

Methods Mentioned

BETA
RNA-seq
Assay

Software Mentioned

COBRA
Gurobi
Systems Biology Markup Language ( SBML )
FBA
GSMM
MOMA
INIT ( Integrative Network Inference for Tissues )
MATLAB
Genewiz
CarveMe

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