Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth
Summary
Accumulating evidence shows that bacteria influence cancer homeostasis, yet the effects of tumor‑associated microbes and their products remain largely unexplored. We previously reported that P. aeruginosa-cancer crosstalk suppresses tumors via the bacterial cupredoxin azurin, and we developed an azurin‑derived peptide that was tested in clinical trials. Building on our previous studies, we studied tumor-resident bacteria for novel therapeutics and targets. Photosynthetic bacteria from the
Content
# Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth
*Published: 2026 Apr 7*
Accumulating evidence shows that bacteria influence cancer homeostasis, yet the
effects of tumor‑associated microbes and their products remain largely
unexplored. We previously reported that P. aeruginosa-cancer crosstalk
suppresses tumors via the bacterial cupredoxin azurin, and we developed an
azurin‑derived peptide that was tested in clinical trials. Building on our
previous studies, we studied tumor-resident bacteria for novel therapeutics and
targets. Photosynthetic bacteria from the phylum Chloroflexota, including a
member of the class Chloroflexia, identified in tumors, carry the cupredoxin
auracyanin gene. Based on the structural and chemical characteristics of
auracyanin, we designed a novel cell-penetrating peptide, aurB. Plant
chloroplasts are thought to have evolved from a bacterial endosymbiont, and both
chloroplasts and mitochondria possess shared proteins essential for
ATP-dependent energy production, indicating that these bacterial-derived
proteins may influence mitochondrial function. Consistent with this model, we
demonstrated that aurB, a peptide from cupredoxin auracyanin B, localized at
mitochondria, blocked energy production by targeting ATP synthase in prostate
cancer cells, thereby significantly inhibiting tumor growth. More strikingly,
combination treatment with aurB and radiation therapy significantly inhibited
tumor growth in a tibial bone metastasis model. Moreover, the number of
metastatic lesions in the lungs was also significantly lower upon aurB
treatment. Multiplex RNA-expression profiling revealed that the inhibition of
ATP production by aurB increased the efficacy of radiation therapy by modulating
multiple pathways involving HIF-1α. Our findings indicate that electron transfer
proteins could represent an important source of promising novel peptide-based
agents that target the aberrantly activated mitochondrial energy system in
cancer.
DOI: 10.1038/s41392-026-02703-7