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Updated: Jun 13, 2026

Measuring Growth and Gene Expression Dynamics of Tumor-Targeted S. Typhimurium Bacteria
Published on: July 6, 2013
Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing
Yoram Barak1, Frank Schreiber, Steve H Thorne
1Department of Microbiology and Immunology, Sherman Fairchild Science Building, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
Background:
Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it.
Methods:
Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro) or using Biosensors (in vivo). Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques.
Results:
SL7838 generated nitric oxide (NO) in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp- and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838.
Conclusions:
NO generation capability is important in the killing of cancer cells by Salmonella strains.
Insights
Salmonella typhimurium bacteria can target and kill cancer cells. Enhanced nitric oxide (NO) generation by these bacteria significantly improves their anti-cancer efficacy, offering a promising therapeutic strategy.
Area of Science:
- Microbiology
- Cancer Biology
- Immunotherapy
Background:
- Bacterial tumor targeting is a key anti-cancer strategy.
- Salmonella typhimurium strain SL7838 demonstrates tumor-targeting and cancer-killing abilities.
- The role of nitric oxide (NO) in bacterial-mediated cancer cell lethality requires further investigation.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) generation in the anti-cancer activity of Salmonella typhimurium.
- To compare the efficacy of different Salmonella strains with varying NO-producing capabilities in cancer therapy.
Main Methods:
- In vitro and in vivo studies were conducted to elucidate the mechanism of Salmonella typhimurium tumor therapy.
- Nitric oxide (NO) levels were measured using chemical assays and biosensors.
- Cancer cell cytotoxicity was assessed using MTS assays, and tumor burden was monitored via molecular imaging.
Main Results:
- Salmonella typhimurium strain SL7838 generated nitric oxide (NO) within cancer cells and tumors.
- A modified strain, SL7842, with enhanced NO production (due to hmp and norV gene deletion), exhibited superior in vitro cancer cell killing and was approximately 100% more effective in treating implanted 4T1 mouse tumors compared to SL7838.
- The enhanced anti-cancer effect of SL7842 was dependent on nitrate availability.
Conclusions:
- The capacity for nitric oxide (NO) generation is crucial for the effectiveness of Salmonella strains in killing cancer cells.
- Engineering Salmonella for enhanced NO production represents a promising strategy for improving bacterial cancer therapy.
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