Structural and molecular investigation of the type IV secretion systems of Gram-positive bacteria

• Grant number: 24/17666-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2025
• End date: April 30, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Pedro Antônio França Henrique
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

Bacteria use different horizontal transfer mechanisms to spread genetic information among themselves, the most common one being conjugation, a process mediated by the type IV secretion system (T4SS). T4SS nanomachines are used not only in conjugation, a process in which ssDNA or dsDNA are translocated from a recipient cell to a donor cell, but also during pathogenesis to translocate proteins such as toxins or protein effectors into humans and animals. Through the process of conjugation, antibiotic resistance genes can propagate among pathogenic strains and thus, T4SSs are important targets to halt the spread of antibiotic resistance genes, a formidable threat to human health. For example, some strains of Enterococcus faecalis and Mycobacterium tuberculosis are pandrug-resistant (PDR), untreatable with known antimicrobial drugs. Our main objective is to understand the conjugation mechanism in Gram positive bacteria, using structural biology approaches. Over the years, Gabriel Waksman's group has made great advances in understanding the mechanism of secretion of T4SSs in Gram-negative bacteria, but very little is known about the structural architecture of the Gram-positive T4SSs. Even though the two share common features, the T4SS machineries are likely to be very different as only a small subset of T4SS components are found in both. Successful conclusion of structural biology work on Gram-positive bacteria will help design new drugs to prevent dissemination of antibiotics resistance genes among Gram-positive bacteria.