Project description:Bovine babesiosis is a tick-borne disease that poses a significant economic threat to cattle industries in tropical and subtropical areas, and Babesia bovis is the most virulent causative agent of bovine babesiosis. This apicomplexan parasite infects erythrocytes of cattle causing severe hemolytic disease, and animals that survive acute infections become persistently infected for life. Young cattle (< 6 months of age) are resistant to infection while adult cattle (>1 year of age) are highly susceptible and succumb to acute infection; however, the immunological mechanisms associated with the age-resistance remain unclear. Protective host immunity involves peripheral blood mononuclear cells (PBMCs) including natural killer (NK) and T cells, and activated macrophages that act to control the pathogen. In this study, we examined the transcriptional signatures of PBMCs from adult cattle (>1.5 years old) experimentally infected with the B. bovis virulent strain S74-T3Bo. Transcriptional signatures evident during the acute phase of babesiosis were categorized into immune-related and non-immune genes. We identified both upregulated and downregulated genes, with fold changes ranging from 2 to 263-fold. We discuss our findings in the context of immune responses to acute disease as a mechanism for adult host survival, with a focus on the molecular functions and biological processes involved in the response to B. bovis infection. In this RNA-Seq analysis, we identified genes related to the immune system, including cytokines and chemokines, complement, cell signaling pathways and surface molecules that may play a role in the recognition of pathogen-associated molecular patterns. In addition, non-immune genes potentially involved in cell proliferation, cell migration, development, energy production, protein-protein interactions, molecular transport, and flagella assembly were also identified.
Project description:Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites; information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.
Project description:Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites; information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. Two-condition experiment, Untreated vs.Treated B. divergens parasites, cultured in human erythrocytes. Treatment with a piperidinyl-benzimidizalone analogue. Biological replicates: 3 untreated (control) replicates, 3 treated replicates. The 6-sample dataset represents untreated(control) vs pooled_reference samples at various timepoints.