Transcriptome and iTRAQ proteomic analysis reveal the molecular mechanism of anti- Candida albicans action of trichoderma acid, a potent novel drug candidate

Candida albicans has become one of the main pathogens of fungal infection, whichcauses great threaten to human health. Hence, it is urgent to develop new anti- C.albicans drugs. A compound named as trichoderma acid was isolated fromTrichoderma spirale , which showed stronger inhibitory effect towards C. albicanseven than positive control nystatin. The transcriptome sequencing and iTRAQ-basedsequencing of trichoderma acid-treated C. albicans were performed to investigate themolecular mechanism of anti- C. albicans. And the most significant differential geneswere verified by qRT-PCR and Western blot analysis. The results indicated that thedisruption of mitochondrial membrane potential, cell membrane, endoplasmic reticulumand the ribosomal in mitochondrial and cell wall were detected in trichoderma acidtreatedC. albicans, resulting in the accumulation of ROS. The expression level ofsupereoxidase SOD was down-regulated, thus enhancing the concentration of ROS.High concentration of ROS led to the DNA damage and destruction of cell skeleton.And the expression levels of Rho-related GTP-binding protein RND3, the asparaginesynthetase ASNS, peroxidases, glutathione S-transferase and heat shock proteinHSP70 were significantly up-regulated in response to the apoptotic process and toxinstimulus, which was demonstrated by Western blot analysis. The transciptomic,proteomic and cellular analysis would provide anti- C. albicans mechanism oftrichoderma acid and the defensive response mechanism of C. albicans.