Metabolic activation of pyruvate cycle by protocatechualdehyde triggers oxidative killing of ampicillin-resistant Escherichia coli

Antimicrobial resistance has emerged as a major global public health threat, underscoring the urgent need for novel therapeutic strategies. In this study, we demonstrate that protocatechualdehyde (PA), a natural compound derived from Salvia miltiorrhiza, exhibits potent and time-dependent bactericidal activity against ampicillin-resistant Escherichia coli, generated through serial passaging of a susceptible Escherichia coli K12 strain . PA was also effective against clinically isolated multidrug-resistant strains of E. coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Furthermore, under the combined effect of PA and aminoglycoside antibiotics, significantly reducing their minimum inhibitory concentrations .