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Salmonella–Host Cell Interactions, Changes in Host Cell Architecture, and Destruction of Prostate Tumor Cells with Genetically Altered Salmonella

Published online by Cambridge University Press:  28 September 2007

Zhisheng Zhong ,
Robert A. Kazmierczak ,
Alison Dino ,
Rula Khreis ,
Abraham Eisenstark  and
Heide Schatten
Zhisheng Zhong
Affiliation:
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, USA
Robert A. Kazmierczak
Affiliation:
Cancer Research Center, Columbia, MO 65201, USA
Alison Dino
Affiliation:
Cancer Research Center, Columbia, MO 65201, USA
Rula Khreis
Affiliation:
Cancer Research Center, Columbia, MO 65201, USA
Abraham Eisenstark
Affiliation:
Cancer Research Center, Columbia, MO 65201, USA
Heide Schatten
Affiliation:
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO 65211, USA
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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.

Keywords

bacteriacancermitochondriacytoskeleton
Type
BIOLOGICAL APPLICATIONS
Information
Microscopy and Microanalysis , Volume 13 , Issue 5 , October 2007 , pp. 372 - 383
Copyright
© 2007 Microscopy Society of America

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