bioRxiv preprint doi: https://doi.org/10.1101/2020.09.25.311100; this version posted September 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated 2 salicylic acid pathway 3 4 Nobuaki Ishihama1, Seung-won Choi1, Yoshiteru Noutoshi2, Ivana Saska1, Shuta Asai1, 5 Kaori Takizawa1, Sheng Yang He3,4, Hiroyuki Osada5, Ken Shirasu1,6 6 7 1Plant Immunity Research Group, RIKEN Center for Sustainable Resource Science, 8 Yokohama, Japan. 9 2Graduate School of Environmental and Life Science, Okayama University, Okayama, 10 Japan. 11 3Department of Energy Plant Research Laboratory, Michigan State University, East 12 Lansing, MI, USA. 13 4Howard Hughes Medical Institute, Michigan State University, East Lansing, MI, USA. 14 5Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 15 Wako, Japan. 16 6Graduate School of Science, The University of Tokyo, Bunkyo, Japan. 17 18 Correspondence to Ken Shirasu (
[email protected]) 19 20 Abstract 21 22 Salicylic acid (SA) and its structural analogs are nonsteroidal anti-inflammatory 23 drugs (NSAIDs) that target mammalian cyclooxygenases. In plants, SA acts as a 24 defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS 25 RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity- 26 related genes. We identified a number of NSAIDs that enhance bacterial effector- 27 induced cell death. Among them, the oxicam-type NSAIDs tenoxicam (TNX), 28 meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory 29 effect on immunity to bacteria and SA-dependent immune responses in plants.