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İnsan babesioz otu protein karakterizasyonu

2022
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Advisor: Doç. Dr. Fatih Kocabaş

Abstract (EN)

Babesia microti, a parasite that causes malaria-like symptoms, is the causative agent of Babesiosis, a protozoan parasite of red blood cells. Human Babesiosis can manifest on a spectrum of severity, ranging from being asymptomatic, and mild-to-moderate severity to being a severe illness that could result in death or incessant relapse. B. microti has increasingly gained resistance against therapeutic drugs. Other than the research mentioned earlier, targeting proteases necessary for the survival of B. microti can be possibly therapeutic, especially the ubiquitin proteasome pathway. The Apicomplexan pathogens that include babesia microti are intercellular parasites, and they are comparable to Crimean Congo Haemorrhagic Fever Virus (CCHFV). Several Viral OTU-related proteins were reported and showed that these proteins have the ability to alter the ubiquitination process and cleave the region of the ISG15 in the infected cells and it was proved that CCHFV has OTU de-ubiquitination activity when cells are invaded. In addition, the OTU deubiquitinase Y89-W99 pockets were determined as having a significant role in developing small molecule inhibitors for treating the diseases. Babesia Microti, an unnamed protein product, was predicted to be from the OTU-like cysteine protease. The results of the present study support the hypothesis that; if the CCHFV can use the deubiquitinase pocket to invade the cells, babesia microti (B.microti) OTU protein can also has the OTU de-ubiquitination activity since there are similarity between CCHFV and Viral OTU-like proteases. This is the first time that babesia microti OTU protein has been identified and characterized. The purpose of this study was to characterize the novel bm-OTU-like protein in vitro and in vivo and mainly its deubiquitination activity. The study represents the first direct demonstration of bm-OTU protease effects on the intracellular ubiquitination at the mono-poly-UB level and cellular immune pathways. Inhibition of this protease activity was planned in this study to develop new approaches for treating babesiosis disease. In conclusion, this study highlights the challenge of protein misfolding and deubiquitination activity of the bm-OTU recombinant protein in vitro and accredits any improvements in different conditions. It can be drawn from all the results shown in this study that the studied recombinant protein has been identified and characterized for any future work in order to develop any new approaches in the field of treatments.

Author

Dr. Betül Yusuf

How to Cite

Betül Yusuf (Master Thesis). İnsan babesioz otu protein karakterizasyonu, 2022, Yeditepe University.

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