Combined Proteomics and Transcriptomics Analysis: Revealing the Antibacterial Mechanism of 1,3,4-Thiadiazole Metal Complexes

Bacterial plant diseases severely threaten agricultural production, necessitating the development of novel and eco-friendly antimicrobial agents. In this study, two thiadiazole metal complexes were rationally designed using a molecular hybridization strategy. Compound T8 displayed outstanding antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo), X. oryzae pv oryzicola (Xoc), and Xanthomonas axonopodis pv citri (Xac) in vitro and in vivo. T8 disrupted bacterial cell wall integrity and enhanced rice defense enzyme activities, effectively inhibiting Xoo proliferation. Integrated proteomic and transcriptomic analyses demonstrated that T8 promoted host mitochondrial respiration and ATP production. Functional experiments revealed that T8 activated the oxidative phosphorylation pathway by enhancing cytochrome c oxidase subunit 6b-1 (COX6b-1) activity. Molecular docking, molecular dynamics simulations, and gene expression analyses further confirmed COX6b-1 as a key mediator. These findings elucidate the molecular basis of T8-induced Xoo resistance and support the development of COX6b-1–protein bactericides.