Potential Anti- Candida albicans Mechanism of Trichoderma Acid from Trichoderma spirale .
Wei YeYuchan ChenWei-Min ZhangTaomei LiuYuping LiuMengran LiSaini LiLiqiong XuHongxin LiuPublished in: International journal of molecular sciences (2023)
Candida albicans is the main causal pathogen of fungal infections in human beings. Although diverse anti- C. albicans drugs have been explored, the drug resistance and side effects of these drugs are intensifying. Thus, it is urgent to explore new anti- C. albicans compounds from natural products. In this study, we identified trichoderma acid (TA), a compound from Trichoderma spirale with a strong inhibitory effect on C. albicans . Transcriptomic and iTRAQ-based proteomic analyses of TA-treated C. albicans in combination with scanning electronic microscopy and reactive oxygen species (ROS) detection were performed to investigate the potential targets of TA. The most significant differentially expressed genes and proteins after TA treatment were verified through Western blot analysis. Our results revealed that mitochondrial membrane potential, endoplasmic reticulum, ribosomes in the mitochondria, and cell walls were disrupted in TA-treated C. albicans , leading to the accumulation of ROS. The impaired enzymatic activities of superoxide dismutase further contributed to the increase in ROS concentration. The high concentration of ROS led to DNA damage and cell skeleton destruction. The expression levels of Rho-related GTP-binding protein RhoE (RND3), asparagine synthetase (ASNS), glutathione S-transferase, and heat shock protein 70 were significantly up-regulated in response to apoptosis and toxin stimulation. These findings suggest that RND3, ASNS, and supereoxide dismutase 5 are the potential targets of TA, as further demonstrated through Western blot analysis. The combination of transcriptomic, proteomic, and cellular analyses would provide clues for the anti- C. albicans mechanism of TA and the defensive response mechanism of C. albicans . TA is thus recognized as a promising new anti- C. albicans leading compound that alleviates the hazard of C. albicans infection in human beings.
Keyphrases
- candida albicans
- reactive oxygen species
- dna damage
- biofilm formation
- cell death
- single cell
- oxidative stress
- endoplasmic reticulum
- binding protein
- endothelial cells
- heat shock protein
- dna repair
- escherichia coli
- stem cells
- rna seq
- south africa
- hydrogen peroxide
- cell cycle arrest
- human health
- gene expression
- high throughput
- induced pluripotent stem cells
- risk assessment
- high speed
- nitric oxide
- resting state
- optical coherence tomography
- heat shock