Functional and structural validation of the citrate binding protein TctC from Bordetella pertussis as a model for mechanistic study of the TTT family

• Grant number: 24/09522-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Leonardo Talachia Rosa
• Grantee: Lívia Barreiro Chiorato
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/11936-6 - The Tripartite Tricarboxylate Transporter (TTT) family: investigating signalling and transport networks in the re-emerging pathogen Bordetella pertussis, AP.JP

Abstract

The gram-negative bacterium Bordetella pertussis is known as the etiologic agent of pertussis, a disease that affects the human respiratory tract, especially children in their first months of life. Immunization against this pathogen can be guaranteed through the administration of the DTPa vaccine, but in recent years a drop in vaccination coverage has been observed, promoting the bacterium to the status of a re-emerging pathogen. One of the main mechanisms for regulating the metabolism of B. pertussis is the presence of the TTT (Tripartite Tricarboxylate Transporter) family, which is made up of the periplasmic protein TctC, responsible for capturing and importing citrate into the bacterial cytoplasmic environment. Although this protein is already known in the bacterial genome, the way in which it is transported to the transmembrane proteins to internalize the substrate has not yet been described at a molecular level. Therefore, this research project aims to study and characterize the transport carried out by the TctC protein of Bordetella pertussis and how this bacterium behaves in the absence of the gene that encodes it. To this end, strategies for expressing the protein of interest, biochemical assays, bioinformatic analyses and microbiological studies will be used to achieve these objectives.