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

Sarcocystosis, caused by parasites within the genus Sarcocystis, is typically asymptomatic but can be associated with myositis, diarrhea, or infection of the central nervous system (CNS). The genus is ancient (relative age, 246 to 500 million years based on small-subunit RNA sequences), diverse (more than 150 catalogued species), highly successful (all vertebrates are susceptible hosts, including fish, birds, reptiles, and mammals), and prevalent (cattle exhibit a 90% infection rate worldwide) (9) . Interestingly, Sarcocystis species are not structurally similar; for example, S. neurona sporozoites, like T. gondii, lack the crystalloid body present in other coccidia, including S. cruzi of cattle (10) . Sarcocystis species typically have a two-host predator-prey life cycle, with one host supporting asexual multiplication while the other acts as the definitive host, supporting a sexual cycle that results in sporocyst shedding in feces. Humans are definitive hosts of S. suihominis and S. hominis and can be infected by S. nesbitti, with associated sequelae, including muscular sarcocystosis. Opossums are the definitive hosts of S. neurona (11) , a species that has a broad intermediate-host range, including raccoons, cats, skunks, and more recently a variety of mustelids, pinnipeds, and cetaceans (12) (13) (14) (15) . S. neurona produces tissue cysts, typically in muscle and occasionally in the CNS (16, 17) . Horses are considered aberrant hosts, in which the parasite typically multiplies as schizonts in the CNS but fails to encyst. Unabated destruction of neural tissue can be fatal to horses and many other hosts, and the disease was called equine protozoal myeloencephalitis before the etiologic protozoan S. neurona was identified and named in 1991 (2) . With migration of opossums to the west coast of North America during the last century (14) the S. neurona host range expanded to cause epizootics in sea otters, harbor seals, and harbor porpoises (18) . S. neurona is now being monitored for its potential as an emerging disease threat. Here, we sequenced and performed a systemsbased analysis of the genome of type II S. neurona strain SO SN1, isolated from a southern sea otter that died of protozoal encephalitis (19) , which represents the most common genotype infecting animals throughout the United States.