Project Title: Structural and functional characterization of the paralogous gene family PFam12 member proteins from the Lyme disease causing agent Borrelia burgdorferi to determine their role in the pathogenesis of Lyme disease

Project No: lzp-2021/1-0068

Period: 1 January 2022 – 31 December 2024

Project costs: 299999,70 EUR

Principle Investigator: Dr.biol. Kalvis Brangulis

Summary

Lyme disease is a common tick-borne infection caused by the spirochete Borrelia burgdorferi, which is transferred from infected Ixodes ticks to the vertebrate host during the ticks’ blood meal. It is the most common tick-borne infectious disease in Europe and the USA. Studies on B. burgdorferi have brought special attention to membrane-associated lipoproteins, since they are likely to play an important role for the bacteria to cause infection. Our recent studies have allowed us to identify that outer surface lipoproteins belonging to the paralogous gene family 12 (PFam12 – BB0844, BBG01, BBH37, BBJ08 and BBK01) are able to bind DNA with high affinity and potentially play an important role in biofilm formation and are important in ensuring the infection. The aim of our project is to comprehensively study the functional and structural properties of PFam12 proteins in order to determine their role in the pathogenesis of Lyme disease and biofilm formation. Some of the methods we will use to achieve our goal include X-ray crystallography to determine protein/protein-DNA 3-d structures; site-directed mutagenesis to characterize protein-DNA interaction; construction of B. burgdorferi PFam12-deficient mutant and evaluation of its influence on the course of infection in mouse models as well as its influence on biofilm formation. The structural and functional characterization of PFam12 proteins is expected to facilitate the development of new strategies to fight against the disease.

Information published 03.01.2022.