In Silico Survey and Characterization of Babesia microti Functional and Non-Functional Proteases.

Monica Florin-Christensen,Sarah N Wieser,Leonhard Schnittger,Carlos E Suarez

doi:10.3390/pathogens10111457

Abstract

Human babesiosis caused by the intraerythrocytic apicomplexan Babesia microti is an expanding tick-borne zoonotic disease that may cause severe symptoms and death in elderly or immunocompromised individuals. In light of an increasing resistance of B. microti to drugs, there is a lack of therapeutic alternatives. Species-specific proteases are essential for parasite survival and possible chemotherapeutic targets. 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 nonactive protease homologs. These proteases can be classified into cysteine (n = 28), serine (n = 21), threonine (n = 14), asparagine (n = 7), and metallopeptidases (n = 19), which, in turn, are assigned to a total of 38 peptidase families. Comparative studies between the repertoire of B. bovis and B. microti proteases revealed differences among sensu stricto and sensu lato Babesia parasites that reflect their distinct evolutionary history. Overall, this data may help direct future research towards our understanding of the biology and pathogenicity of Babesia parasites and to explore proteases as targets for developing novel therapeutic interventions.

Highlights

Human babesiosis caused by Babesia microti is a malaria-like tick-borne zoonotic disease, first described in the 1950s in the USA, with an increasing number of cases reported ever since in this and other countries around the world [1]
The present study aims to shortlist the proteases encoded in the B. microti genome by organizing the information available in the MEROPS protease database, as well as identifying additional peptidases by homology searches for paralogs within the B. microti genome and orthologs of previously described active proteases of B. bovis [26]
The present study shows that the B. microti genome encodes for at least 64 active proteases and 25 non active protease homologs

Summary

Introduction

Human babesiosis caused by Babesia microti is a malaria-like tick-borne zoonotic disease, first described in the 1950s in the USA, with an increasing number of cases reported ever since in this and other countries around the world [1]. The recommended therapeutic drugs to treat B. microti infections are azithromycin plus atovaquone as the first choice or a combination of clindamycin and quinine as an alternative [7,8]. The reported appearance of B. microti parasites resistant to the first two drugs in chronically infected patients and the negative side effects of the latter two call for the development of alternative therapeutic strategies and increased investments in this field [2,7,8,9,10]

Methods

Results

Conclusion