Systems-Based Analysis of the <italic toggle="yes">Sarcocystis neurona</italic> Genome Identifies Pathways That Contribute to a Heteroxenous Life Cycle
Tomasz Blazejewski,
Nirvana Nursimulu,
Viviana Pszenny,
Sriveny Dangoudoubiyam,
Sivaranjani Namasivayam,
Melissa A. Chiasson,
Kyle Chessman,
Michelle Tonkin,
Lakshmipuram S. Swapna,
Stacy S. Hung,
Joshua Bridgers,
Stacy M. Ricklefs,
Martin J. Boulanger,
Jitender P. Dubey,
Stephen F. Porcella,
Jessica C. Kissinger,
Daniel K. Howe,
Michael E. Grigg,
John Parkinson
Affiliations
Tomasz Blazejewski
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
Nirvana Nursimulu
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
Viviana Pszenny
Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA
Sriveny Dangoudoubiyam
Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA
Sivaranjani Namasivayam
Department of Genetics, University of Georgia, Athens, Georgia, USA
Melissa A. Chiasson
Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA
Kyle Chessman
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
Michelle Tonkin
Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
Lakshmipuram S. Swapna
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
Stacy S. Hung
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
Joshua Bridgers
Department of Genetics, University of Georgia, Athens, Georgia, USA
Stacy M. Ricklefs
U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA
Martin J. Boulanger
Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
Jitender P. Dubey
U.S. Department of Agriculture, Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, Beltsville, Maryland, USA
Stephen F. Porcella
Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA
Jessica C. Kissinger
Department of Genetics, University of Georgia, Athens, Georgia, USA
Daniel K. Howe
Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA
Michael E. Grigg
Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, Maryland, USA
John Parkinson
Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario, Canada
ABSTRACT Sarcocystis neurona is a member of the coccidia, a clade of single-celled parasites of medical and veterinary importance including Eimeria, Sarcocystis, Neospora, and Toxoplasma. Unlike Eimeria, a single-host enteric pathogen, Sarcocystis, Neospora, and Toxoplasma are two-host parasites that infect and produce infectious tissue cysts in a wide range of intermediate hosts. As a genus, Sarcocystis is one of the most successful protozoan parasites; all vertebrates, including birds, reptiles, fish, and mammals are hosts to at least one Sarcocystis species. Here we sequenced Sarcocystis neurona, the causal agent of fatal equine protozoal myeloencephalitis. The S. neurona genome is 127 Mbp, more than twice the size of other sequenced coccidian genomes. Comparative analyses identified conservation of the invasion machinery among the coccidia. However, many dense-granule and rhoptry kinase genes, responsible for altering host effector pathways in Toxoplasma and Neospora, are absent from S. neurona. Further, S. neurona has a divergent repertoire of SRS proteins, previously implicated in tissue cyst formation in Toxoplasma. Systems-based analyses identified a series of metabolic innovations, including the ability to exploit alternative sources of energy. Finally, we present an S. neurona model detailing conserved molecular innovations that promote the transition from a purely enteric lifestyle (Eimeria) to a heteroxenous parasite capable of infecting a wide range of intermediate hosts. IMPORTANCE Sarcocystis neurona is a member of the coccidia, a clade of single-celled apicomplexan parasites responsible for major economic and health care burdens worldwide. A cousin of Plasmodium, Cryptosporidium, Theileria, and Eimeria, Sarcocystis is one of the most successful parasite genera; it is capable of infecting all vertebrates (fish, reptiles, birds, and mammals—including humans). The past decade has witnessed an increasing number of human outbreaks of clinical significance associated with acute sarcocystosis. Among Sarcocystis species, S. neurona has a wide host range and causes fatal encephalitis in horses, marine mammals, and several other mammals. To provide insights into the transition from a purely enteric parasite (e.g., Eimeria) to one that forms tissue cysts (Toxoplasma), we present the first genome sequence of S. neurona. Comparisons with other coccidian genomes highlight the molecular innovations that drive its distinct life cycle strategies.
