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Updated: Aug 7, 2025

Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024
Babesia divergens egress from host cells is orchestrated by essential and druggable kinases and proteases
Brendan Elsworth1, Caroline Keroack1, Yasaman Rezvani2
1Harvard T.H. Chan School of Public Health.
Abstract:
Apicomplexan egress from host cells is fundamental to the spread of infection and is poorly characterized in Babesia spp., parasites of veterinary importance and emerging zoonoses. Through the use of video microscopy, transcriptomics and chemical genetics, we have implicated signaling, proteases and gliding motility as key drivers of egress by Babesia divergens. We developed reverse genetics to perform a knockdown screen of putative mediators of egress, identifying kinases and proteases involved in distinct steps of egress (ASP3, PKG and CDPK4) and invasion (ASP2, ASP3 and PKG). Inhibition of egress leads to continued intracellular replication, indicating exit from the replication cycle is uncoupled from egress. Chemical genetics validated PKG, ASP2 and ASP3 as druggable targets in Babesia spp. All taken together, egress in B. divergens more closely resembles T. gondii than the more evolutionarily-related Plasmodium spp. We have established a molecular framework for biological and translational studies of B. divergens egress.
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