Antimicrobial activity and mechanism of gallic acid- gadolinium complex against multidrug-resistant Salmonella

Plant polyphenols, particularly lignin-derived polyphenols, exhibit considerable potential in the development of novel antimicrobial agents against multidrug-resistant (MDR) pathogenic bacteria, but their application has been limited by the inherent instability and low bactericidal activity. Here, we developed a high-efficiency and low-resistance strategy for combating MDR bacteria based on gallic acid (GA)- gadolinium (Gd) complex. The antibacterial circle diameters of GA, Gd, and GA-Gd against Salmonella enterica 6819 were 10.50, 16.25 and 24.15 mm, when initial inoculum was 1 × 10⁸ CFU/mL, indicating that the combination of GA and Gd synergistically enhances their bactericidal activity. Additionally, GA-Gd showed potent antibacterial activity against two sensitive and ten MDR Salmonella strains with the low minimum inhibitory concentration (0.5 mmol/L) and minimum bactericidal concentration values (1.0 mmol/L). GA-Gd can disrupt bacterial wall, membrane, and DNA, contributing to its efficient antibacterial activity. Notably, the RNA-seq analysis showed that GA-Gd downregulated drug resistance genes related to biofilm formation, cationic antimicrobial peptides resistance, beta-lactam resistance and vancomycin resistance. These results suggest that GA-Gd is a promising antibacterial agent to address the threat of antibiotic resistance and MDR Salmonella infections.