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 <b>T8</b> displayed outstanding antibacterial activity against <i>Xanthomonas oryzae</i> pv <i>oryzae</i> (<i>Xoo</i>), <i>X. oryzae</i> pv <i>oryzicola</i> (<i>Xoc</i>), and <i>Xanthomonas axonopodis</i> pv <i>citri</i> (<i>Xac</i>) <i>in vitro</i> and <i>in vivo</i>. <b>T8</b> disrupted bacterial cell wall integrity and enhanced rice defense enzyme activities, effectively inhibiting <i>Xoo</i> proliferation. Integrated proteomic and transcriptomic analyses demonstrated that <b>T8</b> promoted host mitochondrial respiration and ATP production. Functional experiments revealed that <b>T8</b> 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 <b>T8</b>-induced <i>Xoo</i> resistance and support the development of COX6b-1-protein bactericides.