Structural and functional study of LIC11567 and LIC11568, possible toxins of the type II secretion system in Leptospira interrogans Copenhageni Fiocruz L1-130

• Grant number: 23/03653-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2023
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Daniel Enrique Sánchez Limache
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a zoonosis transmitted by contact with environments contaminated by pathogenic bacteria of the genus Leptospira. These Gram-negative bacteria have a two-step protein transporter for the external environment, called the type II secretion system (T2SS). Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130, has a T2SS cluster consisting of 17 genes (LIC_11567 - LIC_11583), of which only 11 are responsible for forming the secretion machinery. The first two genes in the cluster (LIC_11567 and LIC_11568) as well as the last four (LIC_11580 - LIC_11583) may be possible toxins secreted by the system to promote some kind of bacterial competition or interact with host cells favoring bacterial infection. Preliminary analyses with LIC_11567 showed that it is a lipoprotein found in serum of severe leptospirosis patients. Preliminary data from our group and the target of study of this project, LIC_11567 can cause pyroptosis in macrophages and be targeted to the cell nucleus. LIC_11568 has a domain of the M23 family of metallopeptidases, which act with degradation of the cell wall of Gram-positive bacteria, and LysM domain with the ability to bind to peptideoglycan or glycoproteins of the extracellular matrix. Proteins containing the M23 peptidase domain can act as a virulence factor. Based on the data obtained by our group and described above, both genes may be possible toxins secreted by T2SS. Thus, the aim of this PhD project is the functional and structural study of the protein encoded by gene LIC_11567 and the functional study of the protein encoded by gene LIC_11568, located at the beginning of the T2SS cluster of L. interrogans serovar Copenhageni strain Fiocruz L1-130. (AU)