Genome-Scale Metabolic Modeling Reveals Metabolic Alterations of Multidrug-Resistant Acinetobacter baumannii in a Murine Bloodstream Infection Model
570
0303 health sciences
genome-scale metabolic modeling
QH301-705.5
610
<i>Acinetobacter baumannii</i>
Article
3. Good health
transcriptomics
03 medical and health sciences
Acinetobacter baumannii; genome-scale metabolic modeling; transcriptomics; bacteremia; RNA-seq
bacteremia
RNA-seq
Biology (General)
info:eu-repo/classification/ddc/004
DOI:
10.3390/microorganisms8111793
Publication Date:
2020-11-16T16:04:20Z
AUTHORS (10)
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 infection in vivo. Our findings provide important mechanistic insights into the adaption of A. baumannii to the host environment and thus will contribute to the development of new therapeutic agents against this problematic pathogen.
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