Metabolic Responses to Polymyxin Treatment in Acinetobacter baumannii ATCC 19606: Integrating Transcriptomics and Metabolomics with Genome-Scale Metabolic Modeling

Abstract

Combating antimicrobial resistance has been highlighted as a critical global health priority. Due to the drying drug discovery pipeline, polymyxins have been employed as the last-line therapy against Gram-negative “superbugs”; however, the detailed mechanisms of antibacterial killing remain largely unclear, hampering the improvement of polymyxin therapy. Our integrative modeling using the constructed genome-scale metabolic model i ATCC19606 and the correlative multiomics data provide the fundamental understanding of the complex metabolic responses to polymyxin treatment in A. baumannii at the systems level. The model i ATCC19606 may have a significant potential in antimicrobial systems pharmacology research in A. baumannii .