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Caged-hypocrellin mediated photodynamic therapy induces chromatin remodeling and disrupts mitochondrial energy metabolism in multidrug-resistant Candida auris

Summary

Researchers developed a new photodynamic therapy treatment using a light-activated compound called COP1T-HA to fight drug-resistant Candida auris infections. The therapy works by reorganizing the fungal cell’s genetic material architecture and disrupting energy production in mitochondria, ultimately killing the fungal cells. This approach represents a novel strategy to overcome antibiotic resistance, as it targets multiple cellular processes rather than a single pathway that fungi can easily resist.

Background

Candida auris is a multidrug-resistant fungal pathogen causing significant mortality in healthcare settings. Antimicrobial photodynamic therapy (aPDT) using light-activated photosensitizers to generate reactive oxygen species shows promise against C. auris, but its molecular mechanisms remain poorly understood.

Objective

This study investigates how COP1T-HA-mediated photodynamic therapy affects three-dimensional chromatin architecture and gene expression in multidrug-resistant C. auris, with focus on mitochondrial energy metabolism disruption.

Results

PDT induced dose-dependent chromatin remodeling including A/B compartment transitions, TAD reorganization, and chromatin loop disruption. HD-PDT caused pronounced changes in chromatin topology affecting mitochondrial energy metabolism genes. QCR10 and NDUFA5 knockouts showed impaired growth, mitochondrial damage, and reduced ATP production with compensatory glycolysis.

Conclusion

PDT-induced chromatin remodeling directly impacts mitochondrial energy metabolism genes, disrupting the electron transport chain and cellular energy production. This study provides the first 3D genome map of C. auris and establishes chromatin-targeted mechanisms as a novel antifungal strategy against drug-resistant fungi.
  • Published in:Redox Biology,
  • Study Type:Experimental Research,
  • Source: 40544603
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