Systems-Based Analysis of the Sarcocystis neurona Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle

Blazejewski, Tomasz; Nursimulu, Nirvana; Pszenny, Viviana; Dangoudoubiyam, Sriveny; Namasivayam, Sivaranjani; Chiasson, Melissa A.; Chessman, Kyle; Tonkin, Michelle; Swapna, Lakshmipuram S.; Hung, Stacy S.; Bridgers, Joshua; Ricklefs, Stacy M.; Boulanger, Martin J.; Dubey, Jitender P.; Porcella, Stephen F.; Kissinger, Jessica C.; Howe, Daniel K.; Grigg, Michael E.; Parkinson, John

Finally, only two dense-granule (GRA) protein homologs of T. gondii, GRA10 and GRA12, were identified. The discovery of the latter is surprising, given that it has not been annotated in the N. caninum genome. In addition, like the ROPKs, the majority of the GRA proteins encoded by T. gondii that specifically target host immune signaling pathways to alter parasite pathogenesis are not encoded by S. neurona. These include GRA6, which regulates the activation of the host transcription factor nuclear factor of activated T cells (NFAT4); GRA15, which regulates NF-B activation (40); GRA24, which promotes nuclear translocation of host cell p38a MAP kinase (41) ; and the phosphoprotein GRA25, which alters CXCL1 and CCL2 levels to regulate immune responses and control parasite replication (42) . These data indicate either that a different suite of GRA proteins facilitate Sarcocystis host and niche specialization or that Sarcocystis does not require an expanded repertoire of GRA proteins during merozoite replication since it replicates in the host cytosol and is not contained within a PV, like T. gondii or N. caninum.