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Bactericidal bissulfone B7 targets bacterial pyruvate kinase to impair bacterial biology and pathogenicity in plants

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Abstract

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.

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Acknowledgement

This work was supported by the National Key Research and Development Program of China (2022YFD1700300), Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023), and the Key Technologies R&D Program of Guizhou Province in China (2017-5788-1)

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  1. 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

    Awei Zhang, Haizhen Zhang, Ronghua Wang, Hongfu He, Baoan Song & Runjiang Song

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  1. Awei Zhang
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  2. Haizhen Zhang
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  3. Ronghua Wang
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  4. Hongfu He
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Zhang, A., Zhang, H., Wang, R. et al. Bactericidal bissulfone B7 targets bacterial pyruvate kinase to impair bacterial biology and pathogenicity in plants. Sci. China Life Sci. 67, 391–402 (2024). https://doi.org/10.1007/s11427-023-2449-1

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