Rossouw Ingrid, Maritz-Olivier Christine, Niemand Jandeli, van Biljon Riette, Smit Annel, Olivier Nicholas A, Birkholtz Lyn-Marie
Department of Genetics, University of Pretoria, Pretoria, South Africa.
Department of Biochemistry, Centre for Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa.
PLoS Negl Trop Dis. 2015 May 8;9(5):e0003711. doi: 10.1371/journal.pntd.0003711. eCollection 2015 May.
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.
人类巴贝斯虫病，尤其是由源自牛的分歧巴贝斯虫寄生虫引起的病例正在增加，这使得人们重新关注这种可能危及生命的新发人畜共患病。这些寄生虫病理生理学和红细胞内发育的分子机制仍知之甚少。这阻碍了旨在发现新型抗巴贝斯虫药物的协同努力。通过应用敏感的细胞生物学和分子功能基因组学工具，我们描述了分歧巴贝斯虫寄生虫在红细胞内的发育周期，从不成熟的单核环状体到双核配对梨形虫，最终到多核四联虫，这是人畜共患巴贝斯虫属的特征。这首次与人红细胞内发育过程中核含量的增加相关联，为人类感染期间发生的生命周期部分提供了见解。高内涵时间评估阐明了不同阶段对生命周期进展的贡献。此外，分子描述表明分歧巴贝斯虫寄生虫对体外培养采用生理适应性。此外，在寄生虫在其生命周期中平衡其发育阶段时观察到差异表达。总之，这些信息提供了对分歧巴贝斯虫寄生虫功能转录组的首次时间评估，这些信息可能有助于识别对寄生虫生存至关重要的生物学过程，以用于未来抗巴贝斯虫药物的发现。
