Babesia divergens and Babesia microti species-specific genes that may drive pathogenesis

Human babesiosis is an emerging disease as more cases are being reported worldwide. Most cases in Europe are caused by Babesia divergens, whereas most cases in North America are due to Babesia microti. While B. microti is also found throughout Europe, it appears to be less pathogenic. We generated high-quality nuclear and organellar genome assemblies of two B. divergens and two B. microti isolates from Germany by long-read sequencing and compared them with each other and with the reference RI B. microti from the US. Variants of VESA1 (variant erythrocyte surface antigen 1) and secreted antigen 1/3 dominated the genes of the B. divergens isolates. The B. microti isolates and RI B. microti lacked VESA1. However, the B. microti isolates were different by their lack of 37 other proteins found in RI B. microti. These RI-specific proteins were intracellular, secreted, and membrane-bound. The lack of one or more of these genes by the new B. microti isolates may be the reason for why US strains are more pathogenic than B. microti from Europe. The ability of B. divergens to evade the immune system using VESA1, perhaps in combination with some secreted antigens, may be responsible for its higher pathogenicity compared with the European B. microti strains. This study has improved our understanding of the pathogenesis of babesiosis, and the new genomic data provided here has increased the repertoire of available genomic information about Babesia, especially since our new B. microti genomes are the first from Europe.