Study on the role of the serine protease Tsh on innate immune system evasion and the pathogenesis of Sepsis caused by Escherichia coli

• Grant number: 21/14854-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date until: June 01, 2022
• End date until: October 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Waldir Pereira Elias Junior
• Grantee: Miriam Dibo
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/14821-7 - Exploring novel virulence strategies in Escherichia coli, AP.TEM

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are an important cause of infections in humans and their ability to establish an extraintestinal infection is related to the presence of virulence factors. Among the virulence factors produced by ExPEC, the Serine Proteases Autotransporters of Enterobacteriaceae (SPATEs) play important role. They are classified into two classes, called I and II, based on their cytotoxic or immunomodulatory activities, respectively. Among the class II SPATEs, Tsh (temperature-sensitive hemagglutinin) can be highlighted. Initially described in avian pathogenic E. coli (APEC) strains, mediating the hemagglutination capacity presented by some of these strains. However, further studies identified the proteolytic capacity of Tsh at its active serine protease motif, so that this protein is considered to be bifunctional. Although Tsh was initially described in APEC, several studies have reported the presence of the tsh gene in isolates from human extraintestinal infections, and it is important to understand the role that SPATE can play in infections promoted by ExPEC. In this context, the objective of this project is to evaluate the activity of Tsh in the evasion capacity of E. coli from the innate immune system and in the pathogenesis of Sepsis. Understanding the role of Tsh in these infections may bring future perspectives for the treatment and control of these pathogens as agents of serious systemic infections. (AU)