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In this study, we report that caffeine, implanted through a transgenic approach, enhances resistance against variable biotic stresses in rice without fitness cost. Caffeine\u2010producing rice (CPR) was generated by introducing three N\u2010methyltransferase genes involved in the biosynthesis of caffeine in coffee plants. The CPR plants have no differences in morphology and growth compared to their wild\u2010type counterparts, but they show strongly enhanced resistance to both bacterial leaf blight, rice blast, and attack of white\u2010backed planthoppers. Caffeine acts as a repellent agent against rice pathogens. Moreover, caffeine triggers a series of Ca<jats:sup>2+<\/jats:sup> signalling\u2010like processes to synthesize salicylic acid (SA), a hormone associated with plant resistance. In CPR, phosphodiesterase was inhibited by caffeine, cAMP and cGMP increased, intracellular Ca<jats:sup>2+<\/jats:sup> increased, phenylalanine lyase (PAL) was activated by OsCPK1, and SA synthesis was activated. This finding is a novel strategy to improve resistance against the biotic stresses of crops with a special type of defense inducer.<\/jats:p>","DOI":"10.1111\/pce.14273","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T05:12:55Z","timestamp":1643605975000},"page":"1049-1064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Intracellular Ca<sup>2+<\/sup> accumulation triggered by caffeine provokes resistance against a broad range of biotic stress in rice"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0799-7742","authenticated-orcid":false,"given":"Jong\u2010Chan","family":"Park","sequence":"first","affiliation":[{"name":"Department of Genetic Engineering and Graduate School of Biotechnology Kyung Hee University Yongin Republic of Korea"},{"name":"Institute of Crop Biotechnology Kyung Hee University Yongin Republic of 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