BMC Microbiology· 2026Q1
Paraclostridium bifermentans S1-GT1 spores: a novel approach for oncolytic therapy
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- 2026year
Short summary
Paraclostridium bifermentans S1-GT1 spores effectively reduced tumor growth and induced necrosis in preclinical models, with no observed toxicity in mice.
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Key points
- P. bifermentans S1-GT1 spores grow efficiently in hypoxic conditions (<1% oxygen).
- Intratumoral or intravenous spore administration in mice led to tumor necrosis and reduced Ki67-positive cells.
- No adverse effects on feeding, drinking, or survival were observed in mice treated with spores.
- Spore treatment in 4T1-luc tumors reduced bioluminescence signals, indicating an oncolytic effect.
- Transcriptomic analysis showed upregulation of immune-related pathways and collagen genes linked to tissue repair.
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Abstract
The core regions of solid tumors are characterized by hypoxia, which limits the efficacy of conventional therapies. Anaerobic bacterialspores represent a promising therapeutic strategy because they can germinate and proliferate in hypoxic regions. This study evaluatedthe antitumor potential of Paraclostridium bifermentans ( P. bifermentans ) S1-GT1. The strain was characterized by genomic analysis and assessment of sporulation and growth under hypoxic conditions. In vivo safetywas evaluated in mice, and antitumor effects were investigated in MC38 and 4T1-luc tumor-bearing mice. Tumor necrosis, Ki67-positive cells, bioluminescence signals, bacterial distribution in major organs, and transcriptomic changes were examined. P. bifermentans S1-GT1 exhibited strong sporulation, with a genome size of 3,524,444 bp encoding 3,357 protein-coding sequences.Both vegetative cells and spores demonstrated efficient growth under oxygen concentrations below 1%. Mice receiving spores showedno significant adverse effects on feeding, drinking, or survival. In MC38 tumor-bearing mice, intratumoral or intravenous sporeadministration induced tumor necrosis, with no vegetative cells detected in major organs. Spore treatment induced liquefaction ofnecrotic tumor regions and markedly reduced Ki67-positive cells. Additionally, in 4T1-luc tumor-bearing mice, bioluminescenceimaging revealed a marked reduction in tumor-associated signals following intratumoral spore injection, demonstrating a potentoncolytic effect. Transcriptomic analysis revealed upregulated immune-related pathways, including chemotactic factors, complementproteins, and collagen genes linked to necrotic tissue repair, in the spore group. P. bifermentans S1-GT1 exhibits tumor hypoxia-specific growth, oncolytic effects, immune-related responses, and potential safety,supporting its further investigation as a candidate for solid tumor therapy.
The authors' abstract, as published at the source. BMC Microbiology, 2026 · DOI ↗
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BiotechnologyBiochemistry, Genetics and Molecular Biology