Novel Mandelic Acid Derivatives Containing 1,3,4-Oxadiazolyl Thioether for Enhancing Antibacterial Potential against Ralstonia solanacearum

Bacterial wilt caused by Ralstonia solanacearum causes severe crop losses, yet effective agrochemicals remain scarce. Here, we designed a T3SS-targeting antivirulence agent that attenuates the pathogen virulence without inhibiting growth. Two series of mandelic acid and 2-amino-2-phenylacetic acid derivatives containing 1,3,4-oxadiazolyl thioethers were synthesized. High-throughput screening identified W40 (2-(4-chlorophenyl)-2-hydroxy- N -(5-((4-methylbenzyl)thio)-1,3,4-oxadiazol-2-yl)acetamide), which strongly inhibited hrpY expression without affecting bacterial growth. W40 exhibited significant protective activity against R. solanacearum infection in tomato and casuarina. qRT-PCR analysis showed that W40 suppressed T3SS-associated regulatory networks by downregulating key regulators, including prhG, phcA, prhA, and prhR . Phenotypic assays revealed that W40 impaired swimming motility but did not affect the extracellular cellulase activity, biofilm formation, or exopolysaccharide production. These findings highlight W40 as a promising lead compound for antivirulence therapy against bacterial wilt.