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• First report on Colletotrichum cairnsense as causal agent of coffee antrachnose. • Trichoderma asperellum GD040 has antifungal effect and mycoparasitism ability. • Root application of T. asperellum GD040 reduces the lesion caused by C. cairnsense. • T. asperellum GD040 raises the expression of disease-resistance genes in coffee. Coffee anthracnose is an important disease around the world, which has seriously affected the profits of coffee growers. This study firstly reported Colletotrichum cairnsense as a pathogen to cause coffee anthracnose, and screened Trichoderma asperellum GD040 with good antagonistic (inhibition rate was 88.41%) and mycoparasitism ability. Root irrigation with T. asperellum GD040 spore suspension reduces lesion size caused by C. cairnsense on coffee leaves. Transcriptomic analysis showed that the expression of 175 genes in T. asperellum GD040 treated coffee was up-regulated, including 73 disease-resistance genes involved in the plant-pathogen interaction pathway, phenylpropanes biosynthesis pathway and other pathways, respectively. Results from qRT-PCR analysis indicated that the expression levels of 16 key resistance genes (11 disease-resistance genes reported in Coffea canephora , 2 phenylalanine biosynthesis-related genes, ETR , PAL , and OPR3) and 3 growth hormone synthesis-related genes (Pin-1 , SUAR , and GAs-30-O) were up-regulated remarkably in coffee leaves treated by T. asperellum GD040, and were significantly higher than those in coffee leaves inoculated with C. cairnsense. Findings of this study revealed the antagonistic mode of T. asperellum GD040 against C. cairnsense and the mechanism of inducing host resistance in coffee against anthracnose at the molecular level, which laid the foundation for the development of multifunctional Trichoderma biological agents and their application in managing coffee anthracnose. [ABSTRACT FROM AUTHOR]