Grantor: Croatian Science Foundation
Project duration: 2023. do 2027.
Total funding: 199.031,17 EUR
Project team
Principal investigator:
- prof. dr. sc. Marina Šantić dipl. sanit. ing.
Research team:
- prof. dr. sc. Maja Abram, dr.med
- Mateja Ožanič
- doc. dr.sc. Mirna Mihelčić dr. med. vet.
- dr.sc. Ina Viduka mag.sanit.ing.
- dr. sc. biomed. Maša Knežević. mag. pharm. inv.
Brief description:
Francisella tularensis is a gram-negative bacterium, the causative agent of the zoonotic disease tularemia. Tularemia has been reported primarily in areas near water sources. Our and other in vitro studies have shown that F. Tularensis subsp. Tularensis, F. holarctica and F. novicida can replicate in Achantamoeba Castellanii and Hartmannella vermiformis making amoebae an Important environmental reservoir for bacteria. However, it is not known for how long Francisella can survive In amoebae cysts and the mechanisms of survival and recovery in mammalian cells. We hypothesize that the process of transformation of amoebae from the trophozoite stage to cysts is regulated entirely by Francisella. We expect to find the optimal conditions for recovery of bacteria from cysts In different conditions. Our goal Is to determine, in mice model, whether Francisella cultured in an amoeba cyst would elicit an enhanced or reduced Immunological response. Based on our preliminary results, we expect to demonstrate that Francisella species postpone apoptosis and Initiate the autophagy cycle for long¬term survival in cysts. In addition, we will apply the proteomic approach to study the phenotype of Francisella that changes as the amoebae transforms from trophozoite to cyst. To understand the changes In gene expression throughout the life cycle of Francisella in amoebae, the novel method of transcriptomics will be used. Three Francisella species, Francisella tularensis subsp. holarctica strain LVS, F. philomiragia and F. novicida and A. castellanll will be included in this study. In the proposed project, we will combine advanced techniques to identify novel virulence factors of Francisella based on their Intracellular life In amoebae/cysts for successful infection cycle in mammalians. The project will help increase the number of highly qualified young researchers with experience working with emergent Infectious and important public health pathogens.