Transcriptional dynamics in the protozoan parasite Sarcocystis neurona and mammalian host cells after treatment with a specific inhibitor of apicomplexan mRNA polyadenylation

In recent years, a class of chemical compounds (benzoxaboroles) that are active against a range of parasites has been shown to target mRNA polyadenylation by inhibiting the activity of CPSF73, the endonucleolytic core of the eukaryotic polyadenylation complex. One particular compound, termed AN3661, is active against several apicomplexan parasites that cause disease in humans. In this study, we report that AN3661 is active against an apicomplexan that causes disease in horses and marine mammals (Sarcocystis neurona), with an approximate IC50 value of 14.99 nM. Consistent with the reported mode of action of AN3661 against other apicomplexans, S. neurona mutants resistant to AN3661 had an alteration in CPSF73 that was identical to a mutation previously documented in AN3661-resistant Toxoplasma gondii and Plasmodium falciparum. AN3661 had a wide-ranging effect on poly(A) site choice in S. neurona, with more than half of all expressed genes showing some alteration in mRNA 3’ ends. This was accompanied by changes in the relative expression of more than 25% of S. neurona genes and an overall 5-fold reduction of S. neurona transcripts in infected cells. In contrast, AN3661 had no discernible effect on poly(A) site choice or gene expression in the host cells. These transcriptomic studies indicate that AN3661 is exceedingly specific for the parasite CPSF73 protein, and has the potential to augment other therapies for the control of apicomplexan parasites in domestic animals.

Mieloencefalite protozoária em potros: Relato de casos

Mieloencefalite Protozoária Equina é considerada uma doença neurológia de importância onde o protozoário causador da doença é o Sarcocystis neurona e é transmitido aos equinos pela via oro-fecal por dejetos dos hospedeiros definitivos, os gambás (Didelphis virginiana e Didelphis albiventris). A doença causa quadro neurológico nos equinos devido à ação direta do parasita no tecido nervoso, causando resposta inflamatória secundária e sinais clínicos como atrofia muscular assimétrica, fraqueza muscular, incoordenação motora decorrente da diminuição da propriocepção. Os sinais da doença podem variar, pois vai depender da localização da lesão (cérebro, cerebelo ou ainda medula espinhal). Foram atendidos pelo Hospital Veterinário da Universidade de Mato Grosso, dois equinos portadores da doença. O tratamento de escolha foi realizado por meio de toltrazuril, sulfa/trimetoprim, anti-inflamatórios não esteroidais, tiocolchicosido e vitamina E e selênio. Contudo, a melhor forma de prevenção é evitar a contaminação do alimento pelo hospedeiro definitivo.

Evidence for Unknown Sarcocystis-Like Infection in Stranded Striped Dolphins (Stenella coeruleoalba) from the Ligurian Sea, Italy

Two striped dolphins (SD1, SD2), stranded along the Ligurian coast of Italy, were diagnosed with a nonsuppurative meningoencephalitis associated with previously undescribed protozoan tissue cysts. As tissue cysts were morphologically different from those of Toxoplasma gondii, additional histopathological, immunohistochemical, ultrastructural, and biomolecular investigations were performed, aiming to fully characterize the organism. Histopathology revealed the presence of large Sarcocystis-like tissue cysts, associated with limited inflammatory lesions in all CNS areas studied. IHC was inconclusive, as positive staining with polyclonal antisera did not preclude cross-reaction with other Sarcocystidae coccidia. Applied to each animal, 11 different PCR protocols precluded a neural infection by Sarcocystis neurona, Sarcocystis falcatula, Hammondia hammondi, and Neospora caninum. T. gondii coinfection was confirmed only in dolphin SD2. Sarcocystis sp. sequences, showing the highest homology to species infecting the Bovidae family, were amplified from SD1 myocardium and SD2 skeletal muscle. The present study represents the first report of Sarcocystis-like tissue cysts in the brain of stranded cetaceans along with the first description of Sarcocystis sp. infection in muscle tissue of dolphins from the Mediterranean basin.

Sarcocystis neurona and related Sarcocystis spp. shed by opossums (Didelphis spp.) in South America

Protozoan parasites of the genus Sarcocystis are obligatory heteroxenous cyst-forming coccidia that infect a wide variety of animals and encompass approximately 200 described species. At least four Sarcocystis spp. (S. falcatula, S. neurona, S. lindsayi and S. speeri) use opossums (Didelphis spp.) as definitive hosts, and two of them, S. neurona and S. falcatula, are known to cause disease in horses and birds, respectively. Opossums are restricted to the Americas, but their distribution in the Americas is heterogeneous. Five Didelphis spp. are distributed in South America (D. aurita, D. albiventris, D. marsupialis, D. imperfecta and D. pernigra) whereas just one opossum species (D. virginiana) is found in North America. Studies conducted in the last decades show that Sarcocystis spp., derived from South American Didelphis spp., have biological and genetic differences in relation to Sarcocystis spp. shed by the North American opossum D. virginiana. The aim of this review was to address the peculiar scenario of Sarcocystis species shed by South American opossums, with a special focus on diagnosis, epidemiology, and animal infections, as well as the genetic characteristics of these parasites.