Metal-Dependent Hydrolase 1 Encoded by “ <i>Candidatus</i> Liberibacter Asiaticus” Interferes with Citrus Immunity by Targeting Papain-like Cysteine Proteases

Citrus Huanglongbing (HLB), caused by "<i>Candidatus</i> Liberibacter asiaticus" (CLas), is a devastating citrus disease worldwide, and its pathogenesis remains poorly understood. Here, we investigated the virulence function of a Sec-dependent effector, metal-dependent hydrolase 1 (MDH1), which is significantly upregulated in citrus during CLas infection compared to in psyllids. Overexpression of <i>MDH1</i> in citrange reduced its resistance to <i>Xanthomonas citri</i> subsp. <i>citri</i>. RNA-seq and RT-qPCR analyses revealed that <i>MDH1</i> reprogramed the transcription of genes involved in plant-pathogen interactions and suppressed the expression of defense-related genes. Crucially, MDH1 interacted with the <i>Citrus sinensis</i> aleurain-like protease (ALP), a papain-like cysteine protease (PLCP), specifically with the cysteine protease domain. MDH1 also interacted with other PLCP family members and significantly inhibited the expression of several PLCP family genes. This study uncovers how MDH1 suppresses plant immunity by interacting with citrus PLCPs, providing useful information for designing targeted inhibitors to combat HLB.