Silver Nanoparticles Induced Metabolic Perturbations in Pseudomonas Aeruginosa: Evaluation Using the UPLC-QTof-MSE Platform.

Silver nanoparticles (AgNPs) have been widely utilized in various biomedical and antimicrobial technologies, displaying broad-spectrum activities against Gram-negative and Gram-positive bacteria including multidrug-resistant strains. However, the emergence of resistance to AgNPs upon repeated exposure and the survival of bacteria after initial exposure to antimicrobial agents pose a threat, as they may lead to the development of new resistant populations. To combat the early stages of antibacterial resistance, systematic analysis is essential to understand the immediate response of bacteria to antimicrobial agents. In this study, green-synthesized AgNPs with a diameter of approximately 14 nm were exposed toPseudomonas aeruginosaat three different inhibitory concentrations and at two different time intervals (1 and 4 h) to investigate the perturbations in the metabolome using liquid chromatography-high-resolution mass spectrometry. MetaboAnalyst 5.0 was employed for univariate and multivariate analysis, and the affected metabolic pathways were constructed using a variable important in projection scores above 1 from PLS-DA. The study revealed significant alterations in metabolites associated with cell wall synthesis, energy metabolism, nucleotide metabolism, the TCA cycle, and anaplerotic intermediates of the TCA cycle. Our investigation aimed to comprehensively understand the effects of green-synthesized AgNPs onP. aeruginosa metabolism, providing a more precise snapshot of the bacterium's physiological state through metabolomics approach.