The important role of Atg5 in the pathogenesis of tularemia

Joint Meet on 19^th International Conference and Exhibition on Materials Science and Chemistry & 34^th International Conference on Nanomaterials and Nanotechnology

March 26-27, 2021 WEBINAR

Ina Kelava, Mirna Mihelcic, Mateja Ozanic, Valentina Marecic, Maaa Knezevic, Marija Curlin, Sanja Stifter, Anders Sjostedt and Marina Santic

University of Rijeka, Croatia
University of Zagreb, Croatia
Umeå University, Sweden

Scientific Tracks Abstracts: Bioceram Dev Appl

Abstract :

Statement of the Problem: Francisella tularensis is a gram-negative, facultative intracellular bacterium that causes tularemia in humans and animals. Francisella escapes the phagosome early after infection and reaches the macrophage cytosol where the bacteria replicate. After the replication, bacteria re-enter the double-membrane vacuole via autophagy. The role of autophagy in the replication of this cytosolic pathogen has not been fully elucidated. Previous studies showed that Francisella avoids degradation via autophagy mechanism in vitro. Also, Atg5-independent autophagy provides nutrients that support Francisella intracellular replication in vitro. Although the previous studies showed the role of autophagy in the in vitro models, the in vivo role is unknown. Methodology & Theoretical Orientation: We explored the role of Atg5- dependent autophagy on Francisella infection in vivo, by using mice deficient for Atg5 in the myeloid lineage. We determined intracellular replication of F. tularensis strain LVS in the lung, liver, and spleen of Atg5 deficient mice, as well as histopathological changes within the organs in comparison to the control group. Also, we determined the localization of bacteria within the autophagic vacuole during the infection. Findings: Intradermal infection Atg5-deficient mice resulted in significantly reduced bacterial burden and less severe histopathological changes in the lung, liver, and spleen tissues. Conclusion & Significance: We showed for the first time the in vivo role of Atg5-dependent autophagy in the pathogenesis of tularemia. We demonstrated that Atg5 supports Francisella intracellular growth and affects the pathology of the tissues in vivo.

Biography :

Ina Kelava is a young scientist and third-year PhD Student at the Department of Microbiology and Parasitology at the University of Rijeka, Faculty of Medicine. Her PhD work is related to exploring the intracellular lifestyle of Francisella tularensis within different phagocytic and nonphagocytic cells, focusing on the mechanism of autophagy on F. tularensis. She performs in vitro experiments with cell cultures, as well as in vivo experiments on mice using laboratory technics as PCR, q RT-PCR, ELISA, immunohistochemistry, and flow cytometry analyses. She has already published 4 papers.