Evaluation of the anti-eukaryotic activity of T6SS effectors from Salmonella spp. using yeast

• Grant number: 21/13972-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2022
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Ethel Bayer Santos
• Grantee: Luize Nóbrega e Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/02178-2 - Function of type VI secretion systems of pathogenic bacteria in the interaction with eukaryotic cells, AP.JP

Abstract

The type VI secretion system (T6SS) is a protein complex that injects effector proteins into several cell types, including rival bacteria and eukaryotic cells. This pool of effectors represents a reservoir of proteins with a wide range of biochemical activities. Antibacterial effectors are natural antimicrobials, and effectors with anti-eukaryotic activities act against environmental predators and phagocytes of the immune system. Salmonella spp. comprise important pathogens encoding phylogenetically distinct T6SSs acquired via distinct horizontal transfer events. Previous works have shown the importance of S. Typhimurium T6SS in host colonization, but no effector with activity against eukaryotic cells has been identified so far. Using in silico approaches, our group identified putative anti-eukaryotic effectors. The aim of this project is to clone some of these candidates and carry out toxicity assays in eukaryotic cells, using Saccharomyces cerevisiae as a model organism. By the end of this project, we expect to be closer to the understanding of the mechanism by which T6SSs contribute to the pathogenesis of Salmonella spp.