Salmonella typhimurium, like many other intracellular pathogens, is capable of inducing its own uptake into non-phagocytic cells by a process termed invasion, and residing within a membrane-bound inclusion. During invasion it causes significant rearrangment of the host cytoskeleton, indicating that signals are transduced between the bacterium and the host cell cytoplasm, across the eukaryotic cell membrane. We found that intracellular inositol phosphate concentrations in HeLa cells increased during S. typhimurium entry and returned to normal levels after bacterial internalization. A chelator of intracellular calcium (BAPTA / AM) blocked S. typhimurium uptake into HeLa epithelial cells, but extracellular calcium chelators (BAPTA, EGTA, EDTA) had no effect on bacterial invasion. These results indicate that S. typhimurium may activate host cell phospholipase C activity to form inositol phosphates which in turn stimulate release of intracellular calcium stores to facilitate bacterial uptake.
Bibliographical noteFunding Information:
We would like to thank M. Gold for helpful discussions about measuring 1P production. This work was supported by the Medical Research Council of Canada. B.B.F. is a recipient of an International Research Scholars Award from the Howard Hughes Medical Institute, and I.R. is supported by a long term fellowship from the European Molecular Biology Organization (EMBO).
- Inositol phosphate
- Salmonella typhimurium
- Signal transduction