Chemical signaling via histidine kinase sensor QseC and virulence in Enteroaggregative Escherichia coli 042 prototype strain

• Grant number: 19/24231-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2020
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Cristiano Gallina Moreira
• Grantee: Carollina Mazza Abramo Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Enteroaggregative Escherichia coli (EAEC) is an important bacterial pathogen responsible for cases of acute and persistent diarrhea worldwide. To date, several virulence factors of plasmid and chromosomal origin have been described, and the formation of a thick biofilm is a remarkable feature in this category. However, isolates have distinct sets of these factors, so it is an extremely heterogeneous group. Bacteria employ chemical signaling mediated by 2-component systems to regulate its survival mechanisms. In human enteropathogens, the QseBC system is widely distributed, acting directly in the regulation of virulence gene expression of several human pathogens, such as Escherichia coli enterohemorragic, Salmonella Thipymurium, among others. QseC, the bacterial inner membrane sensor, responds to host stress hormones Epinephrine (Epi) and Norepinephrine (NE), as well as to Autoinducer-3 (AI-3), produced by bacteria. Thus, cytoplasmic response regulator QseB is activated and regulates a cascade response directly involved in the development of pathogenesis. The aim of this study is to investigate the chemical signaling mediated by histidine kinase sensor QseC in the virulence of the EAEC 042 prototype strain, in vitro and in vivo, using the alternative model of Galleria mellonella. The qseC gene knockout will be performed via the pJP5603 suicide vector for phenotypic characterization, as well as in vivo assays to evaluate the course of infection in the absence of qseC. Besides opening perspectives to study a new target in this category and the development of therapies in the future.