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Updated: Jul 11, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Salmonella-host cell interactions, changes in host cell architecture, and destruction of prostate tumor cells with
Zhisheng Zhong1, Robert A Kazmierczak, Alison Dino
1Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, USA.
Abstract:
Increasingly, genetically modified Salmonella are being explored as a novel treatment for cancer because Salmonella preferentially replicate within tumors and destroy cancer cells without causing the septic shock that is typically associated with wild-type S. typhimurium infections. However, the mechanisms by which genetically modified Salmonella strains preferentially invade cancer cells have not yet been addressed in cellular detail. Here we present data that show S. typhimurium strains VNP20009, LT2, and CRC1674 invasion of PC-3M prostate cancer cells. S. typhimurium-infected PC-3M human prostate cancer cells were analyzed with immunofluorescence microscopy and transmission electron microscopy (TEM) at various times after inoculation. We analyzed microfilaments, microtubules, and DNA with fluorescence and immunofluorescence microscopy. 3T3 Phi-Yellow-mitochondria mouse 3T3 cells were used to study the effects of Salmonella infestation on mitochondria distribution in live cells. Our TEM results show gradual destruction of mitochondria within the PC-3M prostate cancer cells with complete loss of cristae at 8 h after inoculation. The fluorescence intensity in YFP-mitochondria-transfected mouse 3T3 cells decreased, which indicates loss of mitochondria structure. Interestingly, the nucleus does not appear affected by Salmonella within 8 h. Our data demonstrate that genetically modified S. typhimurium destroy PC-3M prostate cancer cells, perhaps by preferential destruction of mitochondria.
Insights
Genetically modified Salmonella show promise for cancer therapy by targeting tumors. These bacteria destroy prostate cancer cells, primarily by damaging mitochondria, without causing harmful septic shock.
Area of Science:
- Oncology
- Microbiology
- Cell Biology
Background:
- Genetically modified Salmonella are investigated as cancer treatments due to their tumor-homing and cancer-killing properties.
- Wild-type Salmonella infections can cause septic shock, a risk mitigated by specific genetic modifications.
Purpose of the Study:
- To elucidate the cellular mechanisms by which genetically modified Salmonella strains invade and destroy prostate cancer cells.
- To investigate the impact of Salmonella infestation on the ultrastructure of cancer cells, particularly mitochondria.
Main Methods:
- Immunofluorescence microscopy and transmission electron microscopy (TEM) were used to analyze Salmonella-infected PC-3M prostate cancer cells.
- Fluorescence microscopy assessed microfilaments, microtubules, and DNA, while YFP-mitochondria-transfected cells visualized mitochondrial changes.
Main Results:
- Salmonella strains VNP20009, LT2, and CRC1674 were observed invading PC-3M prostate cancer cells.
- TEM revealed gradual destruction of mitochondria within cancer cells, with complete loss of cristae by 8 hours post-inoculation.
- Mitochondrial structure degradation was confirmed by decreased fluorescence in YFP-mitochondria-transfected cells; nuclei remained unaffected within 8 hours.
Conclusions:
- Genetically modified Salmonella effectively destroy PC-3M prostate cancer cells.
- The primary mechanism of cancer cell destruction appears to be the preferential targeting and destruction of mitochondria by Salmonella.
