Modelling the cytosolic [Ca2+] responses induced by Shigella invasion in epithelial cells

Proceedings of The International Conference on Innovation in Bioinformatics and Biomedical Engineering

Year: 2018 | Page No:1


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Modelling the cytosolic [Ca2+] responses induced by Shigella invasion in epithelial cells

R. Ornelas-Guevara,B. Wacquierb, V. González-Vélez and G. Dupont



Shigellosis is an important problem of public health worldwide. It is mainly caused by the ingestion of contaminated food or water contaminated with Shigella. After its ingestion, this bacterium invades the colon and causes an intense inflammatory reaction, leading to destruction of the epithelial tissue. During cell invasion, Shigella induces atypical Ca2+ signals, but its role in invasion has remained unclear and poorly studied (Tran Van Nhieu et al., 2013).
It is well known that every cell type uses Ca2+ as a second messenger to control a wide array of cellular functions, including reorganisation of the cytoskeleton, inflammatory responses and cellular death (Sun et al., 2017). The perturbation of cellular Ca2+ homeostasis caused by Shigella facilitates the entrance of the bacteria and its dispersion to adjacent cells. This further leads to apoptosis and destruction of the intestinal epithelium. The bacterium induces local responses, described as an increase of Ca2+ localised in the invasion area (Tran Van Nhieu et al., 2013), and global responses, that spread in the whole invaded cell. The local versus global character of the responses plays a crucial role in the cytotoxicity of the bacteria, as a high and sustained Ca2+ elevation could lead to cellular death and limit the dissemination of the bacteria. Preliminary work was carried out by Tran Van Nhieu et al. (2013) and Sun, et al (2017) in order to analise the atypical Ca2+ responses induced by Shigella using modeling tools. Nevertheless, the models that have been proposed don’t take into account the Ca2+ coming from the extracellular space, which has been demonstrated to have a crucial contribution to the Ca2+ responses. Thus, in this work we present a partial differential equation (PDE) model that takes into account extracellular Ca2+ entry through Plasma Membrane Channels, as well as Ca2+ and InsP3 diffusion through the cytosol and the conditions caused by Shigella, in order to analise the global vs local character of the cytosolic [Ca2+] responses during bacterial invasion. Numerical simulations show the impact of the plasma membrane channels in the local/global character of the [Ca2+] responses, which implies that controlling extracellular Ca2+ entry to the cytosol could be crucial in order to find a mechanism to limit the dissemination of the bacteria.

Keywords: Calcium signalling, mathematical modelling, transport phenomena, systems biology, StoreOperated Calcium Entry.