Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions

Abstract

Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution.

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis

“…32,33 Although limited in geographic representation, our study represents one of the only comprehensive examinations of babesiois in the upper midwest and the differences observed here may be related to regional genetic variations in the parasite that may affect virulence expression and clinical presentation of disease. 3,34 Importantly, there were no mortalities in this cohort although 10% or greater mortality has been previously described for hospitalized or immunocompromised patients. 2,10,16 In summary, providers should maintain a high degree of suspicion for babesiosis in patients with potential exposure in endemic areas, particularly since incidence appears to be increasing and the risk of severe illness increases with a delay to treatment start of more than 7 days.…”

Theileria parasites subvert E2F signaling to stimulate leukocyte proliferation

“…Jaccard-filtered eukaryotic clusters of orthologous genes (KOGs) were generated as described previously 19 , using the following genomes from EuPathDB (August 25 th , 2014) 20 : Babesia bovis T2Bo, Cryptosporidium hominis TU502, Cryptosporidium muris RN66, Cryptosporidium parvu, Iowa II, Neospora caninnum Liverpool, Plasmodium falciparum 3D7, Plasmodium knowlesi strain H, Plasmodium vivax Sal-1, Theileria annulata strain Ankara, Theileria equi strain WA, and Theileria orientalis strain Shintoku. Also used for creating the KOGs were the updated Theileria parva strain Muguga annotation and an updated Babesia microti RI annotation recently completed by our group 21 . Localization predictions were made with TargetP 22 , transmembrane domain predictions with TMHMM 23 , GPI predictions were made with GPI-SOM 24 , all using the default parameters.…”

Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

“…The BmSA1 full-length gene was amplified from B. microti gDNA by PCR using the specific primers (the sense primer 5 -ATC TAT TCA CTT CTT GCC TGA ACT G-3 and the antisense primer 5 -ATG CCT CCT AAC TGT CAA CTC CG -3 ). The specific primers were designed based on the genome sequence of B. microti (Silva et al, 2016). The thermal cycling parameters included the activation of Taq polymerase at 95 • C for 2 min, 35 cycles of denaturation at 95 • C for 20 s, annealing at 56 • C for 20 s, extension at 72 • C for 25 s, and a final extension of 5 min at 72 • C. Then the full-length gene was cloned into the vector pEASY-Blunt (TransGen Biotech, Beijing, China).…”