Role of Type II Toxin-Antitoxin Systems in the Virulence of Hybrid Escherichia coli BA1250: Insights from a Zebrafish Model

• Grant number: 25/12915-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Roxane Maria Fontes Piazza
• Grantee: Jessika Cristina Alves da Silva
• Supervisor: Matthew A Mulvey
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Utah (U), United States
• Associated to the scholarship: 23/01700-8 - Role of the type II toxin-antitoxin system in the bacterial pathogenesis of a hybrid strain: atypical enteropathogenic Escherichia coli and extraintestinal E. coli, BP.DR

Abstract

Toxin-antitoxin (TA) systems are genetic modules that play critical roles in bacterial stress responses, virulence, and survival under adverse conditions. In Escherichia coli, particularly hybrid strains that combine virulence traits from multiple pathotypes, such as BA1250 in which the functions of TA systems remain poorly characterized. This project focuses on investigating two type II TA systems, YhaV-PrlF and YoeB-YefM, in the pathogenicity of the hybrid E. coli strain BA1250, which carries virulence factors from both atypical enteropathogenic E. coli (aEPEC) and extraintestinal pathogenic E. coli (ExPEC). Although previous studies have linked these systems to bacterial stress responses, their specific contributions to virulence have yet to be elucidated. The project aims to generate mutant strains lacking these TA systems and evaluate their impact on E. coli virulence using the zebrafish (Danio rerio) infection model. Zebrafish offer unique advantages for studying host-pathogen interactions, including genetic homology with humans, optical transparency, and a well-characterized innate immune system. These infection assays will be conducted in collaboration with Dr. Matthew Mulvey's laboratory at the University of Utah, which has extensive expertise in E. coli pathogenesis and zebrafish-based infection models. This internship will provide the candidate with advanced technical training in gene editing and animal infection assays, yield critical data on the role of TA systems in host-pathogen dynamics, and foster international scientific collaboration. The findings will be disseminated through scientific publications, workshops, and integration into ongoing research initiatives at the home institution.