Description
Tuberculosis (TB) is one of the world’s deadliest diseases, claiming millions of lives each year, especially in low- and middle-income countries. Despite years of research, TB remains challenging to diagnose, treat, and prevent. Latency is a remarkable features of TB infection, where Mycobacterium tuberculosis (Mtb) establishes a dynamic equilibrium with the host immune system that lasts for lifetime, although the immunological mechanisms governing the host-pathogen interaction remain poorly understood as are the virulence factors responsible for these unique features.
Mtb genome contains a unique family of genes, the PE_PGRS family containing about 65 members, 51 of which are thought to express functional proteins. They are the largest subgroup of the PE family, which together with the PPE family, unique to mycobacteria, occupy approximately 10% of the Mtb genome coding capacity. PE_PGRSs play critical roles in bacterial pathogenesis and immune evasion. Importantly, PE_PGRSs have shown to influence mycobacterial survival inside macrophages, modulating macrophage type of death and immune functions. However, the molecular mechanism modulating their functions remain enigmatic.
Based on an established collaboration with microbiologists at the Catholic University of Rome, ENIGMA-TB project targets a panel of key PE_PGRS proteins to tackle general features of these important virulence factors, like their localisation and destiny on the bacterial mycomembrane, and their role and contribution in host-pathogen interactions.
Objectives and expected results
The Institute of Biostructures and Bioimaging (IBB-CNR) leads the project, in collaboration with University of Naples “Federico II” and the Catholic University of Rome, bringing together top experts from complementary disciplines in molecular and structural biology, biochemistry and biophysics, with solid experience in infectious diseases and host-pathogen interactions.
The project will leverage the state-of-the-art infrastructure and advanced equipment available at IBB, alongside access to international research facilities. Specifically, IBB will focus on the recombinant production of a panel of PE_PGRS proteins, integrating X-ray crystallography with biophysical and biochemical techniques for structural and functional characterization. The study aims to unravel the mechanisms of action of these enigmatic proteins, providing crucial insights into their role in Mycobacterium tuberculosis pathogenicity, paving the way for significant advancements in the fight against TB.
Project proponents
- Istituto di Biostrutture e Bioimmagini-CNR
Involved entities
- Università degli studi di Napoli “Federico II
Project leader
Dr. Maria Romano (PI)