Biochemistry & Molecular Biology Journal Open Access

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

EuroSciCon conference on Protein, Proteomics and Computational Biology

December 06-07, 2018 Amsterdam, Netherlands

R. Ornelas-Guevara, B. Wacquier, V. Gonzalez-Velez and 4G. Dupont

Process Eng. Posgraduate program (Universidad Autonoma Metropolitana Azcapotzalco, Mexico) Unite de Chronobiologie Theorique (Universite Libre de Bruxelles) Dept. Ciencias Basicas (Universidad Autonoma Metropolitana Azcapotzalco, Mexico)

Posters & Accepted Abstracts: Biochem Mol biol J

Abstract:

Shigellosis is an important problem of public health worldwide. Shigella, the causative agent of Shigellosis, 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. Every cell type uses Ca2+ as a second messenger to control a wide array of cellular functions. Thus, 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, and global responses, that spread in the whole invaded cell. The local/global character of the responses is crucial 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 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 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 to find a mechanism that limit the dissemination of the bacteria.

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