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

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

Content Provider	MDPI
Author	Zhao, Jinxin Zhu, Yan Han, Jiru Lin, Yu-Wei Aichem, Michael Wang, Jiping Chen, Ke Velkov, Tony Schreiber, Falk Li, Jian
Copyright Year	2020
Description	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.
Starting Page	1793
e-ISSN	20762607
DOI	10.3390/microorganisms8111793
Journal	Microorganisms
Issue Number	11
Volume Number	8
Language	English
Publisher	MDPI
Publisher Date	2020-11-16
Access Restriction	Open
Subject Keyword	Microorganisms Biochemical Research Acinetobacter Baumannii Genome-scale Metabolic Modeling Transcriptomics Bacteremia Rna-seq
Content Type	Text
Resource Type	Article

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