Abstract
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.
Highlights
Other parasites like Babesia divergens, who closely resemble malaria parasites, are currently becoming a major concern since these are zoonotically transmitted to humans from their
Human babesiosis is a rapidly emerging, zoonotic, infectious disease causing potentially lifethreatening malaria-like symptoms in humans
Since the symptoms of human babesiosis resemble that of malaria and diagnosis is predominantly reliant on microscopic evaluation of blood smears, this disease may be misdiagnosed as a malaria infection, especially in areas of co-endemicity
Summary
Human babesiosis is a rapidly emerging, zoonotic, infectious disease causing potentially lifethreatening malaria-like symptoms in humans. It is caused by intra-erythrocytic protozoan parasites of the genus Babesia [1] and it is transmitted to humans via an ixodid tick vector or through a blood transfusion from asymptomatic carriers [2]. In Europe, cattle associated B. divergens is the most common causative agent of human babesiosis, especially throughout regions with extensive cattle industries, as the distribution geographically correlates with both pathogen infected host species and tick-vector infested regions, allowing for zoonotic transmission potential [6]. Since the symptoms of human babesiosis resemble that of malaria and diagnosis is predominantly reliant on microscopic evaluation of blood smears, this disease may be misdiagnosed as a malaria infection, especially in areas of co-endemicity. As early reports of resistance against these combinations have been noted in the past few years, the need for alternative treatments is evident [8,9]
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