Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi

Abstract

Apicomplexa tick-borne hemoparasites, including Babesia bovis, Babesia microti, and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis, respectively. These parasites of vast medical, epidemiological, and economic impact have complex life cycles in their vertebrate and tick hosts. Large gaps in knowledge concerning the mechanisms used by these parasites for gene regulation remain. Regulatory genes coding for DNA binding proteins such as members of the Api-AP2, HMG, and Myb families are known to play crucial roles as transcription factors. Although the repertoire of Api-AP2 has been defined and a HMG gene was previously identified in the B. bovis genome, these regulatory genes have not been described in detail in B. microti and T. equi. In this study, comparative bioinformatics was used to: (i) identify and map genes encoding for these transcription factors among three parasites’ genomes; (ii) identify a previously unreported HMG gene in B. microti; (iii) define a repertoire of eight conserved Myb genes; and (iv) identify AP2 correlates among B. bovis and the better-studied Plasmodium parasites. Searching the available transcriptome of B. bovis defined patterns of transcription of these three gene families in B. bovis erythrocyte stage parasites. Sequence comparisons show conservation of functional domains and general architecture in the AP2, Myb, and HMG proteins, which may be significant for the regulation of common critical parasite life cycle transitions in B. bovis, B. microti, and T. equi. A detailed understanding of the role of gene families encoding DNA binding proteins will provide new tools for unraveling regulatory mechanisms involved in B. bovis, B. microti, and T. equi life cycles and environmental adaptive responses and potentially contributes to the development of novel convergent strategies for improved control of babesiosis and equine piroplasmosis.

The Modular Circuitry of Apicomplexan Cell Division Plasticity

“…An additional key insight is that the number of ApiAP2 factors correlates with genome size across the Hemosporidia and Coccidia, and not with the complexity of their life cycles (Oberstaller et al, 2014;Reid et al, 2014;Blazejewski et al, 2015;Woo et al, 2015;Alzan et al, 2016). This is consistent with a general genome scaling law correlation even seen in bacterial systems (Van Nimwegen, 2003).…”

The regulation mechanism of lncRNAs and mRNAs in sea cucumbers under global climate changes: Defense against thermal and hypoxic stresses

“…Moreover, the cell cycle process was the most significantly enriched GO term of the biological processes category, as indicated by the DE-mRNAs in the HT, LO and HL groups. In the current study, topoisomerase II-associated protein (PAT1), a gene that accurately facilitates chromosome separation during cell division (Alzan et al, 2016), showed significantly decreased expression under the three different environmental stresses relative its expression under control conditions (Fig. 2).…”

Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

“…There are diverse mechanisms through which the host defends against this parasitic attack, however, there have been very limited efforts made to understand the process of invasion of the erythrocytes by B. microti parasites and the many molecules associated with this process (Montero et al, 2009 ; Sun et al, 2011 ). The molecules that are involved in this process of invasion are likely to be important virulence factors (Alzan et al, 2016 ) that can be explored as potential candidates for vaccine development or to develop novel therapies, with the ultimate goal of preventing babesiosis and eradicating Babesia parasites. Our research presented here led to several interesting findings, some of which may have direct therapeutic application.…”