Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity

Introduction: Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear. Objectives:...

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Main Authors: Yazhou Bao, Qian Zhang, Hai Zhu, Yong Pei, Yaning Zhao, Yixin Li, Peiyun Ji, Dandan Du, Hao Peng, Guangyuan Xu, Xiaodan Wang, Zhiyuan Yin, Gan Ai, Xiangxiu Liang, Daolong Dou
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Advanced Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2090123224000870
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author Yazhou Bao
Qian Zhang
Hai Zhu
Yong Pei
Yaning Zhao
Yixin Li
Peiyun Ji
Dandan Du
Hao Peng
Guangyuan Xu
Xiaodan Wang
Zhiyuan Yin
Gan Ai
Xiangxiu Liang
Daolong Dou
author_facet Yazhou Bao
Qian Zhang
Hai Zhu
Yong Pei
Yaning Zhao
Yixin Li
Peiyun Ji
Dandan Du
Hao Peng
Guangyuan Xu
Xiaodan Wang
Zhiyuan Yin
Gan Ai
Xiangxiu Liang
Daolong Dou
author_sort Yazhou Bao
collection DOAJ
description Introduction: Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear. Objectives: This study aimed to elucidate MET’s role in inducing plant immunity and investigate the associated mechanisms. Methods: To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay. Results: Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants. Conclusion: Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.
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spelling doaj-art-1f869296c1484a758c635eb8e4e6dadd2025-01-18T05:04:22ZengElsevierJournal of Advanced Research2090-12322025-02-01683141Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunityYazhou Bao0Qian Zhang1Hai Zhu2Yong Pei3Yaning Zhao4Yixin Li5Peiyun Ji6Dandan Du7Hao Peng8Guangyuan Xu9Xiaodan Wang10Zhiyuan Yin11Gan Ai12Xiangxiu Liang13Daolong Dou14College of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, China; College of Plant Protection, China Agricultural University, Beijing 100193, ChinaCollege of Plant Protection, China Agricultural University, Beijing 100193, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, China Agricultural University, Beijing 100193, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, China Agricultural University, Beijing 100193, ChinaUSDA Agricultural Research Service, San Joaquin Valley Agricultural Sciences Center, Parlier, CA 93648, USACollege of Plant Protection, China Agricultural University, Beijing 100193, ChinaCollege of Plant Protection, China Agricultural University, Beijing 100193, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Plant Protection, China Agricultural University, Beijing 100193, China; College of Life Sciences, South China Agricultural University, Guangzhou 510642, China; Corresponding authors at: College of Plant Protection, China Agricultural University, Beijing 100193, China (X. Liang). College of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, China (D. Dou).College of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, China; College of Plant Protection, China Agricultural University, Beijing 100193, China; Corresponding authors at: College of Plant Protection, China Agricultural University, Beijing 100193, China (X. Liang). College of Plant Protection, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing 210095, China (D. Dou).Introduction: Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear. Objectives: This study aimed to elucidate MET’s role in inducing plant immunity and investigate the associated mechanisms. Methods: To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay. Results: Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants. Conclusion: Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.http://www.sciencedirect.com/science/article/pii/S2090123224000870MetforminPlant immunityCPK28Phosphorylation
spellingShingle Yazhou Bao
Qian Zhang
Hai Zhu
Yong Pei
Yaning Zhao
Yixin Li
Peiyun Ji
Dandan Du
Hao Peng
Guangyuan Xu
Xiaodan Wang
Zhiyuan Yin
Gan Ai
Xiangxiu Liang
Daolong Dou
Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
Journal of Advanced Research
Metformin
Plant immunity
CPK28
Phosphorylation
title Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
title_full Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
title_fullStr Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
title_full_unstemmed Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
title_short Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity
title_sort metformin blocks bik1 mediated cpk28 phosphorylation and enhances plant immunity
topic Metformin
Plant immunity
CPK28
Phosphorylation
url http://www.sciencedirect.com/science/article/pii/S2090123224000870
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