Enhanced phenylpropanoid metabolism underlies resistance to f. sp. race 4 infection in the cotton cultivar Pima-S6 ( L.).

f. sp. vasinfectum (FOV) race 4 (FOV4) is a highly pathogenic soil-borne fungus responsible for Fusarium wilt in cotton () and represents a continuing threat to cotton production in the southwest states of the United States, including California, New Mexico, and Texas. Pima ( L.) cotton, which is highly valued for its fiber quality, has been shown to be more susceptible to this pathogen than Upland ( L.) cotton. Still, some Pima cultivars present resistance to FOV4 infection. To gain insights into the FOV4-resistance mechanism, we performed comparative transcriptional and metabolomic analyses between FOV4-susceptible and FOV4-resistant Pima cotton entries. FOV4-resistant Pima-S6 and FOV4-susceptible Pima S-7 and Pima 3-79 cotton plants were infected with FOV4 in the greenhouse, and the roots harvested 11 days post-infection for further analysis. We found that an enhanced root phenylpropanoid metabolism in the resistant Pima-S6 cultivar determines FOV4-resistance. Gene-ontology enrichment of phenylpropanoid biosynthesis and metabolism categories correlated with the accumulation of secondary metabolites in Pima-S6 roots. Specifically, we found esculetin, a coumarin, an inhibitor of Fusarium's growth, accumulated in the roots of Pima-S6 even under non-infected conditions. Genes related to the phenylpropanoid biosynthesis and metabolism, including phenylalanine ammonia-lyase 2 (PAL2) and pleiotropic drug resistance 12 (PDR12) transporter, were found to be upregulated in Pima-S6 roots. Our results highlight an essential role for the phenylpropanoid synthesis pathway in FOV4 resistance in Pima-S6 cotton. These genes represent attractive research prospects for FOV4-disease resistance and breeding approaches of other cotton cultivars of economic relevance.