National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, 550025, China.
Sci China Life Sci. 2024 Feb;67(2):391-402. doi: 10.1007/s11427-023-2449-1. Epub 2023 Nov 17.
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 (B) 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 B. 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 B 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，水稻细菌性条斑病（BLB）的防治尚未实现。在此，我们开发了一系列新型双砜类化合物和一个具有独特机制的新型靶标，以应对这一挑战。所开发的双砜类化合物可以控制稻黄单胞菌（Xoo），其中 2-（双（甲基磺酰基）亚甲基）-N-（4-氯苯基）腙-1-甲酰胺（B）比商业药物噻二唑铜（TC）和双噻唑（BT）更有效。我们首次鉴定出稻黄单胞菌中的丙酮酸激酶（PYK）是我们的双砜类化合物 B 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 B 通过竞争性抑制在转录水平上降低 PYK 的表达，在蛋白质水平上阻断 PYK 的活性，并破坏 PYK-Clp-regR 复合物内的相互作用，从而削弱细菌的生物学和致病性。本研究为针对 PYK 的抗 Xoo 策略的分子和机制方面提供了新的见解。我们相信，这些有价值的发现将用于未来的细菌疾病控制。
