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LATVIAN

BIOMEDICAL

RESEARCH AND STUDY CENTRE

RESEARCH AND EDUCATION IN BIOMEDICINE FROM GENES TO HUMAN

Tick-Borne Pathogens Research Group (K.Brangulis lab)

Our research mainly focuses on the structural and functional analysis of proteins form Borrelia burgdorferi, the causative agent of Lyme disease (Lyme borreliosis). With over 140 different lipoproteins anchored to the membrane via an N-terminal lipid modification, B. burgdorferi, among other bacteria is exceptionally rich in lipoproteins, many of which are exposed on the outer surface. Despite the vital roles these proteins play in the pathogenesis of Lyme disease, the specific ligands or receptors for most of them remain unknown. Using x-ray crystallography, our aim is to solve the structures of individual proteins, as well as the complexes they form with other proteins or ligands. By combining this structural data with functional studies, we aim to enhance our understanding of the molecular mechanisms employed by B. burgdorferi in causing infection. Potentially the acquired knowledge could be used to develop novel strategies to fight against Lyme disease.

Kalvis Brangulis, PhD

Kalvis Brangulis, PhD

Head of the research group, senior researcher

Personnel

Kalvis Brangulis, PhD, kalvis@biomed.lu.lv

Everita Elīna Siņicina, BSc, everita.elina@biomed.lu.lv

Leonora Jankovica, leonora.jankovica@biomed.lu.lv

Linda Laura Paga, linda.paga@biomed.lu.lv

Areas for searching partners

  • Structural and functional studies of the Lyme disease-causing agent proteins
  • Structural and functional studies of proteins associated with other tick-borne pathogens

10 the most representative publications for the scientific group

  1. Brangulis, K.; Akopjana, I.; Bogans, J.; Kazaks, A.; Tars, K., Structural studies of chromosomally encoded outer surface lipoprotein BB0158 from Borrelia burgdorferi sensu stricto. Ticks Tick Borne Dis 2024, 15, (1), 102287. DOI: https://doi.org/10.1016/j.ttbdis.2023.102287
  2. Brangulis, K.; Drunka, L.; Akopjana, I.; Tars, K., Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form. Biochim Biophys Acta Proteins Proteom 2024, 1872, (1), 140969. DOI: https://doi.org/10.1016/j.bbapap.2023.140969
  3. Foor, S. D.; Brangulis, K.; Shakya, A. K.; Rana, V. S.; Bista, S.; Kitsou, C.; Ronzetti, M.; Alreja, A. B.; Linden, S. B.; Altieri, A. S.; Baljinnyam, B.; Akopjana, I.; Nelson, D. C.; Simeonov, A.; Herzberg, O.; Caimano, M. J.; Pal, U., A unique borrelial protein facilitates microbial immune evasion. mBio 2023, 14, (5), e0213523. DOI: https://doi.org/10.1128/mbio.02135-23
  4. Marcinkiewicz, A. L.; Brangulis, K.; Dupuis, A. P., 2nd; Hart, T. M.; Zamba-Campero, M.; Nowak, T. A.; Stout, J. L.; Akopjana, I.; Kazaks, A.; Bogans, J.; Ciota, A. T.; Kraiczy, P.; Kolokotronis, S. O.; Lin, Y. P., Structural evolution of an immune evasion determinant shapes pathogen host tropism. Proc Natl Acad Sci U S A 2023, 120, (27), e2301549120. DOI: https://doi.org/10.1073/pnas.2301549120
  5. Akopjana, I.; Brangulis, K., Structural Analysis of the Outer Membrane Lipoprotein BBA14 (OrfD) and the Corresponding Paralogous Gene Family 143 (PFam143) from Borrelia burgdorferi. Pathogens 2022, 11, (2). DOI: https://doi.org/10.3390/pathogens11020154
  6. Brangulis, K.; Akopjana, I.; Petrovskis, I.; Kazaks, A.; Tars, K., Structural analysis of the outer surface proteins from Borrelia burgdorferi paralogous gene family 54 that are thought to be the key players in the pathogenesis of Lyme disease. J Struct Biol 2020, 210, (2), 107490. DOI: https://doi.org/10.1016/j.jsb.2020.107490
  7. Brangulis, K.; Akopjana, I.; Petrovskis, I.; Kazaks, A.; Zelencova, D.; Jekabsons, A.; Jaudzems, K.; Tars, K., BBE31 from the Lyme disease agent Borrelia burgdorferi, known to play an important role in successful colonization of the mammalian host, shows the ability to bind glutathione. Biochim Biophys Acta Gen Subj 2020, 1864, (3), 129499. DOI: https://doi.org/10.1016/j.bbagen.2019.129499
  8. Brangulis, K.; Akopjana, I.; Petrovskis, I.; Kazaks, A.; Jekabsons, A.; Jaudzems, K.; Viksna, A.; Bertins, M.; Tars, K., Structural analysis of Borrelia burgdorferi periplasmic lipoprotein BB0365 involved in Lyme disease infection. FEBS Lett 2020, 594, (2), 317-326. DOI: https://doi.org/10.1002/1873-3468.13594
  9. Brangulis, K.; Akopjana, I.; Kazaks, A.; Tars, K., Crystal structure of the N-terminal domain of the major virulence factor BB0323 from the Lyme disease agent Borrelia burgdorferi. Acta Crystallogr D Struct Biol 2019, 75, (Pt 9), 825-830. DOI: https://doi.org/10.1107/S2059798319010751