The autophagic cellular process: a possible mechanism of enteroinvasive Escherichia degradation by intestinal epithelial cells

• Grant number: 12/05591-4
• Support type: Regular Research Grants
• Duration: July 01, 2012 - December 31, 2014
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Marina Baquerizo Martinez
• Grantee: Marina Baquerizo Martinez
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The invasion of enteroinvasive Escherichia coli (EIEC) and Shigella sp into intestinal cells is essential in the conduct of bacillary dysentery. The secretion of a set of protein effectors by means of the type III secretion system (TTSS) into the host cell is a precondition for triggering the internalization process. Most of these functions are related to proteins encoded by a 31Kb fragment of the virulence plasmid. Among them, there were icsA and icsB genes which are responsible for the expression of two proteins IcsA and IcsB, necessary for intra and intercellular spread across of the host intestinal epithelium. The recognition of invading bacteria by the host cell is a key component in determining the establishment of bacterial infection. Recent reports have indicated that autophagy, a system of degradation of cytoplasmic organelles and proteins present in the cytosol, including invading bacteria, are crucial for cell survival. However, some species of bacteria such as Shigella flexneri have survival strategies opposite autophagic degradation. It was observed that Shigella, an invasive bacteria was found to be able to escape autophagy by secreting IcsB by means of the TTSS. Mutant bacteria lacking IcsB were trapped by autophagy during multiplication within the host cells. IcsB did not directly inhibit autophagy. Rather, Shigella IcsA, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB binding to IcsA. Recently, in our laboratory was noticed that EIEC icsA and icsB gene expressions and bacteria spread were lower than S. flexneri both in intestinal cells and murine macrophages. Furthermore, experiments with dendritic cells have shown that disease triggered by EIEC is more restricted to a specific site, in other words, it is not able to spread as to extend the tissue damage in a more drastic, as Shigella. Based on the results observed by our group it has been hypothesized that the lower spread of EIEC may be related to its death by autophagy, this mechanism may make EIEC more susceptible to recognition by the host cell. (AU)