Bacteria-derived peptide aurB halts prostate tumour growth by targeting mitochondrial energy production

The peptide ‘aurB’ – derived from a tumour-associated bacteria found in the cancer's microenvironment – has targeted mitochondrial energy production to enhance radiotherapy response in preclinical prostate cancer models

A peptide therapy derived from bacteria resident within tumours has been shown to suppress their growth in preclinical models of prostate cancer, according to investigators at University of Illinois Chicago, Illinois, USA . The approach, which targets mitochondrial energy production, has shown pronounced efficacy when combined with radiotherapy, a standard therapy in the management of prostate cancer.

The treatment centres on a short peptide – aurB – engineered from a fragment of a bacterial protein identified within the tumour microenvironment. In animal models, aurB disrupted mitochondrial function in cancer cells, thereby inhibiting adenosine triphosphate production and depriving tumours of the energy required to sustain rapid proliferation. When used alongside radiation, the peptide has produced a marked reduction in tumour size without observable toxicity.

“Mitochondria are very important for a cell to survive – they are the energy factories,” said Dr. Tohru Yamada, senior author of the study and associate professor in surgery and biomedical engineering.

“Many cancer cells exhibit altered mitochondrial number and activity, because a cancer cell has to grow aggressively and rapidly. Therefore, mitochondria would be an ideal target for cancer therapy,” he said.

The work builds on a growing body of research into the tumour microenvironment, where bacterial populations have long been known to reside. Over recent decades, attention has shifted towards the potential to exploit these microorganisms as a source of anti-cancer agents.

Earlier investigations by Yamada and colleagues identified a class of bacterial proteins known as ‘cupredoxins’ which transport electrons and can modulate tumour growth. A peptide derived from one such protein has previously entered clinical evaluation, including studies in adult patients and paediatric brain cancer.

However, that earlier candidate depended on the tumour suppressor gene p53, a pathway frequently disrupted in cancer and characterised by diverse mutation patterns. This heterogeneity has limited the therapeutic scope of p53-dependent strategies. The present study therefore sought to identify an alternative bacterial-derived mechanism that bypasses p53 and instead targets mitochondrial function directly.

“We wanted to have an anti-cancer agent that doesn’t use the p53 function,” Yamada said.

To achieve this, the research team analysed tumour samples from patients with breast cancer, using DNA sequencing to characterise resident bacterial species. One organism contained a cupredoxin protein known as auracyanin, which shares functional properties with previously characterised proteins but operates through a distinct intracellular pathway. The investigators subsequently engineered aurB to mimic this protein’s activity.

Mechanistic studies have shown that aurB enters tumour cell mitochondria and binds to ATP synthase, a critical enzyme complex responsible for cellular energy generation. By interfering with this process, the peptide effectively induces an energetic crisis within cancer cells. This mechanism has proved effective in cell lines lacking functional p53 and in mouse models of hormone therapy-resistant prostate cancer, which is a disease setting that currently has limited treatment options.

“The combination significantly enhanced the activity of the peptide and the tumour became much smaller,” Yamada said.

“This approach is promising. Using a well-established tibial bone metastatic model, we demonstrated significant inhibition of tumour growth, preclinically,” he added.

The investigators have secured intellectual property protection for aurB through the university’s technology transfer framework and have begun to explore translational pathways, including early-phase clinical trials. If successful, the approach could complement existing radiotherapy regimens by sensitising tumours through metabolic disruption.

Beyond this specific candidate, the study highlights a broader strategy to mine the tumour microbiome for therapeutically relevant molecules. Bacterial proteins such as auracyanin may represent only a small subset of a much larger reservoir of biologically active compounds with potential oncological applications.

“There are many other bacterial proteins that could be source of cancer drugs. We simply haven’t tried them yet,” Yamada concluded.

The project has involved collaboration across clinical and academic departments within the university’s college of medicine and associated health system.

For further reading please visit: 10.1038/s41392-026-02703-7