| Summary: | Nonhost resistance refers to resistance of a plant species to all genetic variants of a non-adapted pathogen. Such resistance has the potential to become broad-spectrum and durable crop disease resistance. We previously employed <i>Arabidopsis thaliana</i> and a forward genetics approach to identify plant mutants susceptible to the nonhost pathogen <i>Phytophthora sojae</i>, which resulted in identification of the T-DNA insertion mutant <i>esp1</i> (<i>enhanced susceptibility to Phytophthora</i>). In this study, we report the identification of VQ motif-containing protein 28 (<i>VQ28</i>), whose expression was highly up-regulated in the mutant <i>esp1</i>. Stable transgenic <i>A. thaliana</i> plants constitutively overexpressing <i>VQ28</i> compromised nonhost resistance (NHR) against <i>P. sojae</i> and <i>P. infestans</i>, and supported increased infection of <i>P. parasitica</i>. Transcriptomic analysis showed that overexpression of <i>VQ28</i> resulted in six differentially expressed genes (DEGs) that are involved in the response to abscisic acid (ABA). High performance liquid chromatography-mass spectrometry (HPLC-MS) detection showed that the contents of endogenous ABA, salicylic acid (SA), and jasmonate (JA) were enriched in <i>VQ28</i> overexpression lines. These findings suggest that overexpression of <i>VQ28</i> may lead to an imbalance in plant hormone homeostasis. Furthermore, transient overexpression of <i>VQ28</i> in <i>Nicotiana benthamiana</i> rendered plants more susceptible to <i>Phytophthora</i> pathogens. Deletion mutant analysis showed that the C-terminus and VQ-motif were essential for plant susceptibility. Taken together, our results suggest that <i>VQ28</i> negatively regulates plant NHR to <i>Phytophthora</i> pathogens.
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