Synergy of ATP and Meropenem in Stimulating the TCA Cycle to Enhance Killing of Carbapenem-Resistant Acinetobacter baumannii.

ABSTRACT: The global prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) represents a substantial concern for public health. Exogenous adenosine triphosphate (ATP) affects the bactericidal efficacy of meropenem against CRAB; however, the precise mechanism remains elusive. Here, reprogramming metabolomics was employed to delve into the mechanism underlying ATP-potentiated meropenem lethality against CRAB. Our findings reveal that ATP reprogramming activates the tricarboxylic acid (TCA) cycle in A. baumannii. Notably, the TCA cycle inhibitor malonate antagonised the synergistic bactericidal effect of ATP and meropenem. Activation of the TCA cycle stimulated riboflavin metabolism pathway and the electron transport chain, leading to increased reactive oxygen species (ROS) production. Hydro

SUBMITTER: Li X 

PROVIDER: S-EPMC12278800 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature