Immune response and chemical signaling upon Citrobacter rodentium infection in vivo

• Grant number: 19/14833-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: October 01, 2019
• End date: February 28, 2020
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Cristiano Gallina Moreira
• Grantee: Karine Melchior
• Supervisor: Manuela Raffatellu
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 18/22042-0 - Chemical signaling and virulence in Escherichia coli enterohemorrhagic mediated by members of the microbiota, BP.MS

Abstract

Diarrheogenic Escherichia coli are human natural pathogens that do not have an animal model widely accepted in the literature, limiting their studies in vivo. Enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC, respectively) are bacteria that possess in their genome the Island of pathogenicity Locus of Enterocyte Effacement (LEE), responsible for encoding virulence genes. The histidine kinase sensor QseC plays an important role in the regulation of this island. Citrobacter rodentium is a natural murine pathogen, which shows 67% similarities of its genes with these human pathogens, including LEE. Since EHEC poorly infects rodents' models, C. rodentium is widely used as an animal infection model to understand the molecular basis of the mechanisms developed in vivo by EHEC and EPEC. Class I-restricted T cell-associated molecules (CRTAM) are adhesins expressed in intraepithelial T cells that contribute to the retention of T cells in the epithelial mucosa. Recent studies have shown that wild-type mice (positive for CRTAM) exhibit increased Th17 responses during infection with gut pathogens. The exacerbated gut inflammation enables the pathogen to take advantage of the gut environment and outcompete the microbiota to grow to higher levels. This study proposal will focus on the chemical signaling through QseC sensor and T cells immunologic response during in vivo infection with C. rodentium, and the consequent changes on the gut microbiota. The infection experiments will be performed in wild-type and Crtam-/- littermate mice with C. rodentium wild-type and the qseC mutant strains. These results will provide a better understanding of how the sensor QseC impacts gut inflammation in mice, and how these differences in chemical signaling between bacteria and host response could shape the microbiota and the course of the disease. (AU)