Transcriptomic analysis of Lasiodiplodia theobromae treated by azithromycin

Tea leaf spot caused by Lasiodiplodia theobromae is an emerging fungal disease that significantly reduces the yield and quality of tea in tea-producing regions owing to the lack of effective control methods. In this study, we evaluated the antifungal activity of azithromycin, a macrolide antibiotic, against L. theobromae. In vitro assays demonstrated strong inhibitory activity, with a half-maximal effective concentration (EC50). Morphological and ultrastructural analyses using optical and transmission electron microscopy revealed that azithromycin induced pronounced hyphal abnormalities, including cytoplasmic disorganisation and membrane disruption. Integrated transcriptomic, proteomic, and metabolomic analyses indicated that azithromycin treatment led to systemic disruptions in L. theobromae, including dysregulation of genes involved in carbohydrate metabolism, protein degradation, glycoprotein and cell wall biosynthesis, ergosterol biosynthesis, mitochondrial function, and stress response pathways. Molecular docking and bioinformatic analyses identified glycoside hydrolase family, a key protein in carbohydrate metabolism, as the principal target of azithromycin. This study offers comprehensive insights into the antifungal mechanism of azithromycin and establishes its potential as a novel agent for integrated management of tea diseases. These results provide a valuable foundation for the development of next-generation fungicides and sustainable disease control strategies for tea cultivation.