Apicomplexan egress from host cells is fundamental to the spread of infection and is poorly characterized in 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 . 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 spp. All taken together, egress in more closely resembles than the more evolutionarily-related spp. We have established a molecular framework for biological and translational studies of egress.
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| http://dx.doi.org/10.21203/rs.3.rs-2553721/v1 | DOI Listing |
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