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Background  As effects of global climate change intensify, the interaction of biotic and abiotic stresses increasingly threatens current agricultural practices. The secondary cell wall is a vanguard of resistance to these stresses.  Fusarium thapsinum  (Fusarium stalk rot) and  Macrophomina phaseolina  (charcoal rot) cause internal damage to the stalks of the drought tolerant C4 grass, sorghum ( Sorghum bicolor  (L.) Moench), resulting in reduced transpiration, reduced photosynthesis, and increased lodging, severely reducing yields. Drought can magnify these losses. Two null alleles in monolignol biosynthesis of sorghum ( brown midrib 6-ref ,  bmr6-ref ; cinnamyl alcohol dehydrogenase, CAD; and  bmr12-ref ; caffeic acid O-methyltransferase, COMT) were used to investigate the interaction of water limitation with  F. thapsinum  or  M. phaseolina  infection.    Results  The  bmr12  plants inoculated with either of these pathogens had increased levels of salicylic acid (SA) and jasmonic acid (JA) across both watering conditions and significantly reduced lesion sizes under water limitation compared to adequate watering, which suggested that drought may prime induction of pathogen resistance. RNA-Seq analysis revealed coexpressed genes associated with pathogen infection. The defense response included phytohormone signal transduction pathways, primary and secondary cell wall biosynthetic genes, and genes encoding components of the spliceosome and proteasome.    Conclusion  Alterations in the composition of the secondary cell wall affect immunity by influencing phenolic composition and phytohormone signaling, leading to the action of defense pathways. Some of these pathways appear to be activated or enhanced by drought. Secondary metabolite biosynthesis and modification in SA and JA signal transduction may be involved in priming a stronger defense response in water-limited  bmr12  plants.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12870-021-03149-5.

Pathogen and drought stress affect cell wall and phytohormone signaling to shape host responses in a sorghum COMT bmr12 mutant