The prevention and control of rice bacterial leaf blight (BLB) disease has not yet been achieved due to the lack of effective agrochemicals and available targets. Herein, we develop a series of novel bissulfones and a novel target with a unique mechanism to address this challenge. The developed bissulfones can control Xanthomonas oryzae pv. oryzae (Xoo), and 2-(bis(methylsulfonyl)methylene)-N-(4-chlorophenyl) hydrazine-1-carboxamide (B₇) is more effective than the commercial drugs thiodiazole copper (TC) and bismerthiazol (BT). Pyruvate kinase (PYK) in Xoo has been identified for the first time as the target protein of our bissulfone B₇. PYK modulates bacterial virulence via a CRP-like protein (Clp)/two-component system regulatory protein (regR) axis. The elucidation of this pathway facilitates the use of B₇ to reduce PYK expression at the transcriptional level, block PYK activity at the protein level, and impair the interaction within the PYK-Clp-regR complex via competitive inhibition, thereby attenuating bacterial biology and pathogenicity. This study offers insights into the molecular and mechanistic aspects underlying anti-Xoo strategies that target PYK. We believe that these valuable discoveries will be used for bacterial disease control in the future.

由于缺乏有效的农药和可用的靶标，水稻白叶枯病（BLB）病害的防治尚未实现。在此，我们开发了一系列新型双砜和具有独特机制的新型靶标来应对这一挑战。开发的双砜类药物可以控制米黄单胞菌pv。oryzae ( Xoo ) 和 2-(双(甲基磺酰基)亚甲基)-N- ( 4-氯苯基)肼-1-甲酰胺 (B ₇ ) 比商业药物噻二唑铜 (TC) 和双甲噻唑 (BT) 更有效。Xoo中的丙酮酸激酶 (PYK)首次被确定为我们的双砜 B ₇的靶蛋白。PYK 通过 CRP 样蛋白 (Clp)/双组分系统调节蛋白 (regR) 轴调节细菌毒力。该途径的阐明有助于使用 B ₇在转录水平降低 PYK 表达，在蛋白质水平阻断 PYK 活性，并通过竞争性抑制损害 PYK-Clp-regR 复合物内的相互作用，从而减弱细菌生物学和致病性。这项研究提供了对针对 PYK 的抗Xoo策略的分子和机制方面的见解。我们相信这些有价值的发现将来将用于细菌性疾病的控制。