Comparative proteomics unveils the bacteriostatic mechanisms of Ga(III) on the regulation of metabolic pathways in Pseudomonas aeruginosa

J Proteomics. 2023 Sep 28:105011. doi: 10.1016/j.jprot.2023.105011. Online ahead of print.ABSTRACTGallium has a long history as a chemotherapeutic agent. The mechanisms of action of Ga(III)-based anti-infectives are different from conventional antibiotics, which primarily result from the chemical similarities of Ga(III) with Fe(III) and substitution of gallium into iron-dependent biological pathways. However, more aspects of the molecular mechanisms of Ga(III) against human pathogens, especially its regulations on bacterial metabolic processes, remain to be understood. Herein, by using conventional quantitative proteomics approaches, we identified the protein changes of Pseudomonas aeruginosa (P. aeruginosa) in response to Ga(NO3)3 treatment. We show that Ga(III) exhibits bacteriostatic mode of action against P. aeruginosa through affecting the expressions of a number of key enzymes in the main metabolic pathways, including glycolysis, TCA cycle, amino acid metabolism, and protein and nucleic acid biosynthesis. In addition, decreased abundances of proteins associated with pathogenesis and virulence of P. aeruginosa were also identified. Moreover, the correlations between protein expressions and metabolome changes in P. aeruginosa upon Ga(III) treatment were identified and discussed. Our findings thus expand the understanding on the antimicrobial mechanisms of gallium that shed light on enhanced therapeutic strategies. BIOLOGICAL SIGNIFICANCE: Mounting evidence suggest that th...
Source: Journal of Proteomics - Category: Biochemistry Authors: Source Type: research