posted on 2024-01-11, 17:41authored byAwei Zhang, Hongfu He, Ronghua Wang, Zhongjie Shen, Zengxue Wu, Runjiang Song, Baoan Song
1,3,4-Oxadiazole thioethers have shown exciting antibacterial
activities;
however, the current mechanism of action involving such substances
against bacteria is limited to proteomics-mediated protein pathways
and differentially expressed gene analysis. Herein, we report a series
of novel 1,3,4-oxadiazole thioethers containing a carboxamide/amine
moiety, most of which show good in vitro and in vivo bacteriostatic activities. Compounds A10 and A18 were screened through CoMFA models as optimums against Xanthomonas oryzae pv. oryzae (Xoo, EC50 values of 5.32 and 4.63 mg/L, respectively)
and Xanthomonas oryzae pv. oryzicola (Xoc, EC50 values
of 7.58 and 7.65 mg/L, respectively). Compound A10 was implemented in proteomic techniques and
activity-based protein profiling (ABPP) analysis to elucidate the
antibacterial mechanism and biochemical targets. The results indicate
that A10 disrupts the growth
and pathogenicity of Xoc by interfering with pathways
associated with bacterial virulence, including the two-component regulation
system, flagellar assembly, bacterial secretion system, quorum sensing,
ABC transporters, and bacterial chemotaxis. Specifically, the translational
regulator (CsrA) and the virulence regulator (Xoc3530) are two effective
target proteins of A10. Knocking
out the CsrA or Xoc3530 gene in Xoc results in a significant reduction in the motility and
pathogenicity of the mutant strains. This study contributes available
molecular entities, effective targets, and mechanism basis for the
management of rice bacterial diseases.