Mitochondrial characteristics of echinocandin tolerance and resistance in Candida glabrata and Candida krusei.

BACKGROUND

Candidiasis, especially candidemia, is one of the most common invasive fungal infections. With the increase of risk factors such as tumors, its high incidence and high mortality rate pose a significant challenge to public health. Echinocandins, as first-line drugs for candidemia, have their clinical efficacy severely weakened by the emergence of tolerant or resistant strains such as Candida glabrata and Candida krusei.

METHODS

The study evaluated the changes in mitochondrial phenotype (intracellular ATP levels, mitochondrial membrane potential, mitochondrial superoxide levels, and intracellular ROS levels), proteomic, metabolomic, and genomic in C. glabrata and C. krusei.

RESULTS

By analyzing strains with different susceptibility profiles, the study found that echinocandin tolerant or resistant strains displayed significant upregulation of ATP levels and unique metabolic adaptations. Quantitative proteomics identified differentially expressed proteins associated with mitochondrial function and energy metabolism. Metabolomic analysis further revealed distinct profiles linking resistance to alterations in purine metabolism and oxidative phosphorylation. Additionally, genomic sequencing of the resistant strains highlighted mutations in key genes involved in ATP binding.

CONCLUSION

These findings highlight the mitochondrial characteristics in echinocandin tolerance and resistance in C. glabrata and C. krusei, providing valuable insights into potential pathways for future therapeutic interventions targeting resistant Candida species.