Role of the autotransporter protein VAT (Vacuolating Autotransporter Toxin) in the pathogenesis of Sepsis caused by Escherichia coli

• Grant number: 22/02861-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): May 01, 2022
• Effective date (End): October 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Waldir Pereira Elias Junior
• Grantee: Claudia Andrade Freire
• 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

The serine proteases autotransporters of the Enterobacteriaceae family (SPATE) are related to virulence functions in E. coli, such as adherence, invasion, cytotoxicity, resistance to serum bactericidal activity and biofilm formation. Members of this family are classified into class I (cytotoxic proteins) and class II (immunomodulatory proteins). VAT protease (vacuolating autotransporter toxin) is a class II SPATE that is cytotoxic to chicken embryonic fibroblast cells and contributes to avian cellulitis infection. VAT is a 140 kDa protein that is processed during translocation to release a 111 kDa passenger domain into the extracellular milieu via the type V secretion system. The VAT gene was originally identified within a pathogenicity island (PAI) designated VAT-PAI in APEC strain Ec222, but later identified in UPEC, EAEC, and EPEC strains. In UPEC VAT is associated with virulence and contributes to survival during systemic infection in a murine model. Our group showed that the SPATE Pic is responsible for the inactivation of key molecules of the complement system. Other authors have reported the lytic action on these molecules of the innate immune system by the SPATE EspP. Recently, we determined in a collection of 266 E. coli strains isolated from bacteremia that the most frequent SPATE genes wee: sat (34%), VAT (28%), pic (8%) and tsh (5%). Since some SPATEs are proteins involved in the evasion of the host's immune system, they are important virulence factors in the pathogenesis of Sepsis caused by E. coli. However, there is a lack of studies related to this family of proteins and their immune evasion action. Therefore, the objective of this study is to evaluate the role of VAT on the mechanisms mediating the complement system evasion. (AU)