In silico survey and characterization of Babesia microti functional and non-functional proteases

Authors: FLORIN-CHRISTENSEN, MONICA - National Institute Of Agricultural Technology(INTA); WIESER, SARAH - National Institute Of Agricultural Technology(INTA); Suarez, Carlos; SCHNITTGER, LEONHARD - National Institute Of Agricultural Technology(INTA)

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/6/2021
Publication Date: 11/10/2021
Citation: Florin-Christensen, M., Wieser, S.N., Suarez, C.E., Schnittger, L. 2021. In silico survey and characterization of Babesia microti functional and non-functional proteases. Pathogens. 10(11). Article 1457. https://doi.org/10.3390/pathogens10111457.
DOI: https://doi.org/10.3390/pathogens10111457

Interpretive Summary: Infections caused by the intraerythrocytic apicomplexan tick-borne parasite Babesia microti in humans are expanding at an alarming rate in the US. The disease that can cause severe symptoms and death in elderly or immunocompromised individuals. There is a shortage of therapeutic alternatives in the context of emergence of resistance to the drugs by B. microti. In this study we defined the set of 64 putative proteases encoded by the genome of the parasite by comparison with other related parasites such as Babesia bovis. Overall, the data generated in this study may help directing future research towards our understanding of the biology and pathogenicity of Babesia parasites, and to explore proteases as targets for developing novel therapeutic interventions.

Technical Abstract: Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that can cause severe symptoms and death in elderly or immunocompromised individuals. There is a shortage of therapeutic alternatives in the context of emergence of resistance to the drugs by B. microti. Species-specific proteases are essential for parasite survival, and a possible chemotherapeutic approach. However, the repertoire of proteases in B. microti remains poorly investigated. Herein, we employed several combined bioinformatics tools and strategies to organize and identify genes encoding for the full repertoire of proteases in the B. microti genome. We identified 64 active proteases and 25 non active protease homologues. These proteases can be classified as cysteine (n=28), serine (n=21), threonine (n=14), aspartic (n=7) and metallo- (n=19) peptidase types and can be assigned to a total of 38 peptidase families. Comparative studies among the B. bovis and B. microti protease repertoire also revealed differences in the protease repertoire among sensu stricto and sensu lato babesia parasites that reflect differences in their evolutionary history. Overall, this data may help directing future research towards our understanding of the biology and pathogenicity of Babesia parasites, and to explore proteases as targets for developing novel therapeutic interventions.