To kill a piroplasm: genetic technologies to advance drug discovery and target identification in Babesia

• Published in: International journal for parasitology 2019-02, Vol.49 (2), p.153-163
• Main Authors: Keroack, Caroline D., Elsworth, Brendan, Duraisingh, Manoj T.
• Format: Article
• Language: English
• Subjects: Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Apicomplexan; Babesia; Babesia - drug effects; Babesia - genetics; Drug Development; Drug discovery; Drug Discovery - methods; Drug target identification; Genetics; Genetics, Microbial - methods; Humans; Target validation
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2018.09.005

[Display omitted] •The poorly understood biology and the large diversity of piroplasmids poses a challenge to drug development.•The ability to culture many Babesia spp. in vitro and in vivo provides an opportunity to identify core, conserved biology.•The availability of many genetic tools in related parasites will help accelerate genetic technology development in Babesia.•The use of sophisticated genetic techniques will be essential for the identification and validation of drug targets. Babesia parasites infect a diverse range of vertebrate hosts, from penguins to pigs. Recently, the emergence of zoonotic Babesia infection has been increasing, and the list of species reported to infect humans continues to grow. Babesiosis represents a burgeoning veterinary and medical threat, and the need for novel therapeutic drugs to effectively target this diverse group of parasites is pressing. Here, we review the current culture systems that exist to study and manipulate Babesia parasites, and identify the scope and methods for target discovery and validation to identify novel, potent anti-babesial inhibitors. Challenges exist including difficulties in the culture systems of important zoonotic parasites, and there is a lack of integrated morphological and molecular data. While molecular approaches in several Babesia spp. has become a reality, the ability to rapidly identify and validate drug targets is hindered by a lack of sophisticated genetic tools to probe parasite biology. The minimal genome size and haploid nature of blood-stage Babesia parasites presents an opportunity to adapt techniques from related systems and characterise the druggable genomic space in a high-throughput way. The considerable diversity of parasites within the genus suggests the existence of highly divergent biology and polymorphism that could present a formidable barrier to the development of a pan-babesiacidal therapeutic strategy.