Functional and structural studies of the protein codified by the gene LIC_11189

• Grant number: 25/22192-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2026
• End date: December 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Ana Julia Chagas Ciappina
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a zoonosis with a major impact on public health, caused by the bacterium Leptospira interrogans. This species exhibits complex mechanisms of adaptation and virulence, regulated in part by intracellular signaling through cyclic nucleotides, such as c-di-GMP. This secondary messenger regulates essential processes for bacterial survival, including motility, biofilm formation, and virulence. The levels of c-di-GMP are controlled by the balance between enzymes responsible for its synthesis (diguanylate cyclases) and degradation (phosphodiesterases). Within this context, recent in silico studies from our research group highlighted the phosphodiesterase encoded by the LIC_11189 gene, which belongs to the HD-GYP family, for presenting a novel structural insertion (HdiD) that may be related to specific regulatory functions. In this one-year project, we aim to clone, express, and structurally and functionally characterize the protein encoded by the locus_tag LIC_11189, employing molecular biology, biochemistry, and crystallography techniques. We expect the results obtained to contribute to a better understanding of the complex regulatory mechanisms of c-di-GMP signaling in Leptospira interrogans, as well as to provide insights for future strategies to control leptospirosis. (AU)