Neospora hughesi

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Neospora hughesi
Scientific classification
Domain:
Eukaryota
Phylum:
Apicomplexa
Class:
Conoidasida
Order:
Eucoccidiorida
Family:
Sarcocystidae
Genus:
Neospora
Species:
N. hughesi
Binomial name
Neospora hughesi
Marsh et al.1998 [1]

Neospora hughesi is an obligate protozoan apicomplexan parasite that causes myelitis and equine protozoal myeloencephalitis (EPM) in horses, and has only been documented in North America. [1] EPM is a neurological disease from lesions in the spinal cord, brain stem, or brain from parasites such as N. hughesi or Sarcocystis neurona . [2] Signs that a horse may have EPM include ataxia, muscle atrophy, difficulty swallowing, and head tilt. [2] There are antiprotozoal drugs, such as the 28-day course of ponazuril, to treat the disease, as well as anti-inflammatories to alleviate neurologic symptoms [2] [3]

Contents

Taxonomy

Neospora hughesi was considered the same parasite as Sarcocystis neurona , Neospora spp. (including N. caninum), and Toxoplasma gondii until the 1970s, when innovations in macromolecular analysis suggested phenotypic and molecular differences, which resulted in the divergence of species. [4] However, it is now observed that both Neospora species and Sarcocystis species cause EPM, with the latter being more common. [4]

N. hughesi is a member of the Apicomplexa phylum, a phylum of mainly parasitic alveolates and obligate intracellular parasites. [4] This phylum also includes the protozoa that cause malaria ( Plasmodium ) and toxoplasmosis ( Toxoplasma ). [4]

Sarcocystis neurona is in the same family as Neospora hughesi and is the most common parasite that causes EPM. Toxoplasma gondii also is in the Sarcocystidae family, and is hallmarked as the feline analogue to S. neurona and N. hughesi. [4] Molecular analysis concluded that N. hughesi is specific to equid species. [4]

Discovery

Etymology

Neospora hughesi is named after one of the discoverers, J.P. Hughes, a veterinary researcher whose interests in toxoplasmosis, sarcocystosis, and neosporosis, led to the differentiation of the aformentioned species. [5] The genus Neospora is Greek for neo, or new, and spora, or seed.

Methods

The first pathogenic Neospora species was first reported to cause paralysis in dogs in 1988, and had therefore been termed Neospora caninum . [1] Successive neonatal and fetal infections caused by Neospora-like protozoa had later been discovered in deer, goats, cattle, and horses. [6] Characterization studies had failed to differentiate canine and bovine isolates, and both were identified as N. caninum based on its similarities in immune responses to viruses and similar internal transcribed spacer (ITS-1) regions. [7] ITSs are sections on nonfunctional RNA in rRNA that precede the genomic transcripts and are often used to detect similarities across species. [7] Only by ITS sequencing was Neospora hughesi discovered. A 1998 paper by Antoinette E. Marsh, Bradd C. Barr, Andrea E. Packham, and Patricia A. Conrad. demonstrates the "ultrastructural, molecular, and antigenic characterization" of an equine Neospora species isolate, NE1. [1] Via transmission electron microscopy (TEM) of parasites isolated from equine spinal cord tissue, E. Marsh et al. discovered a distinct species, Neospora hughesi.

Comparison of N. hughesi to canine and bovine N. caninum isolates revealed phenotypic differences in immunoreactive proteins. [1] In preparation for the TEM, a total of 103 randomly oriented bradyzoite (quiescent parasites) profiles in eight tissue cysts and 69 tachyzoite (actively proliferating parasites) profiles were examined in the host nerve tissue. These NE1 isolates (N. hughesi) were grown in monkey kidney cells, whereas the N. caninum isolate (CN1) was cultured from the central nervous system of a six-week-old Rhodesian ridgeback puppy born with neurological deficits. The puppy had a N. caninum fluorescent antibody test (IFAT) titer to confirm infection. [1] In the study, the bovine N. caninum isolate (BPA1) was cultured under the same conditions as the aforementioned isolates. Viable tachyzoites from all three isolates (CN1, BPA1, and NE1) were harvested from similarly infected monolayers, and the culture medium containing tachyzoites underwent a series of filtering and pelleting steps to isolate the protein and DNA. [1] Uninfected cell monolayer cultures were treated under the same conditions to serve as a negative control. [1] Tachyzoite pellets and the control cells were separated via SDS-PAGE, and purified antigens were transferred to nitrocellulose gel incubated with antibodies to determine molecular characterization via Polymerase Chain Reaction (PCR). [1] PCR amplifies the nuclear small subunit RNA ((nss)-rRNA) so that the ITS-1 regions could be compared amongst the isolates, ultimately deducing that the NE1 isolate is a separate Neospora species, N. hughesi. [1]

Morphology

Apicomplexa have a complex life cycle, whereby they have three infective stages, including an invasive tachyzoite (proliferating), bradyzoite in tissue cysts (quiescent), and sporozoite (environmental) stages. [1] In the definitive host (which is unknown at this time), the parasite undergoes its proliferative cycle in the intestines, ultimately passing unsporulated oocysts (sporozoites) in feces. [8] These oocysts then sporulate from the fecal matter, and when an intermediate host (the horse) ingests them, tachyzoites proliferate and form cellular conglomerates composed of bradyzoites (quiescent cells) in both skeletal and nervous tissues (including the spinal cord). [8] Tachyzoites in the intermediate host (horses) vary in shape from crescent-shaped to round and measure around 7μm by 5μm, and are found in a variety of organs and tissues. [8] N. hughesi tissue cysts are most commonly found in the central nervous system, but can be found in eye muscles or aborted fetuses too. [8] These cysts can measure 100μm in diameter and are constituted of bradyzoites that measure around 7μm by 1.5μm. [8]

Metabolism

The organisms classified under the Apicomplexa phylum possess a unique organelle structure called an apicoplast, which plays a vital role in lipid metabolism. [9] The apicoplast originated from algae through secondary endosymbiosis, resulting in a four-membrane bound plastid that contains its own DNA. [9] The apicoplast genome is comparably small, with a size of 35 kb encoding 30-50 genes which are involved in fundamental cellular processing utilizing DNA and RNA. [9] The Neospora spp. are obligate intracellular parasites, meaning that they hijack host cell machinery to proliferate whilst in the tachyzoite life stage of the parasite. [10]

Genomics

The complete genome of N. hughesi has not yet been sequenced, but partial apicoplast and mitochondrial genomes have been. The largest partial apicoplast genome sequenced is a 440bp linear DNA that encodes for the RNA polymerase beta subunit gene. Among the other sequenced genes are the apicoplast caseinolytic protease C gene and the mitochondrial cytochrome-b gene, responsible for protein regulation and cellular respiration, relatively. [11]

Physiology

N. hughesi is a Gram-positive, obligate intracellular parasite with cocci morphology. [10] N. hughesi contain apicomplexan-specific organelles that secrete enzymes vital for the development of the parasitic vacuole in the host. [12] This parasitic vacuole protects the parasite from host cell defense mechanisms via regulation of secretory organelles. [12]

Apicomplexans also have an inner membrane complex (IMC) that partakes in parasite movement, replication, and invasion of the host. [12] Apicomplexans are aptly named for a specific organelle called an apicoplast, which plays a vital role in lipid metabolism. [9] All specialized organelles are located on the apical side of the parasite, hence the name Apicomplexa.

Ecology and host range

Although there is no definitive host for N. hughesi, it is suggested that horses are infected with N. hughesi by exposure (ingestion) to sporozoites from the feces of the host- the same mechanism as its close sister taxa Sarcocystis neurona and Neospora caninum . [13]

N. hughesi has been implicated as the cause of clinical disease in Equine protozoal myeloencephalitis (EPM) cases. There have been no cases of EPM caused by Neospora species outside of the United States interestingly. [13] It is estimated that EPM causes symptomatic disease in roughly 1% of horses exposed to the sporulated oocysts. [2]

Environmental implications

N. hughesi can cause infection of the central nervous system, EPM. Due to lack of research of N. hughesi and because the host for S. neurona, the opossum, is isolated to the United States only, EPM is not generally considered as a diagnosis differential of horses of non-United States origin. [13] However, given the recent differentiation of N. hughesi from S. neurona, EPM from N. hughesi should be integrated into equine veterinary medicine as a diagnostic differential for neurological symptoms. [14] There have been recent cases of horses imported from North America infected with EPM in the Netherlands and other European countries. [15] This has led to enhanced quarantine measures for imported horses and awareness of EPM and other parasitic-driven diseases in equids.

Infection with N. hughesi has been associated with neuromuscular disease and fetal abortions, but it is not as well studied as Sarcocystis neurona is. Transmission from N. hughesi-infected horses to foals has been reported, but not all will develop clinical disease, as is supported in N. caninum studies in canines and coyotes. [13] With the increased transportation of horses from the United States to other countries, it is critical that more research be conducted to understand the mechanisms and definitive hosts to prevent the spread of N. hughesi before it becomes transmissible in other parts of the world. Currently, the potential of N. hughesi is unknown, so it is worthwhile to determine definitive hosts and implications to prevent an outbreak of neosporosis.

Related Research Articles

<span class="mw-page-title-main">Apicomplexa</span> Phylum of parasitic alveolates

The Apicomplexa are organisms of a large phylum of mainly parasitic alveolates. Most possess a unique form of organelle structure that comprises a type of non-photosynthetic plastid called an apicoplast—with an apical complex membrane. The organelle's apical shape is an adaptation that the apicomplexan applies in penetrating a host cell.

<i>Toxoplasma gondii</i> Species of protozoan parasite

Toxoplasma gondii is a parasitic protozoan that causes toxoplasmosis. Found worldwide, T. gondii is capable of infecting virtually all warm-blooded animals, but felids are the only known definitive hosts in which the parasite may undergo sexual reproduction.

Coccidiosis is a parasitic disease of the intestinal tract of animals caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody in severe cases, is the primary symptom. Most animals infected with coccidia are asymptomatic, but young or immunocompromised animals may suffer severe symptoms and death.

<i>Neospora caninum</i> Species of Conoidasida in the apicomplex phylum

Neospora caninum is a coccidian parasite that was identified as a species in 1988. Prior to this, it was misclassified as Toxoplasma gondii due to structural similarities. The genome sequence of Neospora caninum has been determined by the Wellcome Trust Sanger Institute and the University of Liverpool. Neospora caninum is an important cause of spontaneous abortion in infected livestock.

<span class="mw-page-title-main">Rhoptry</span>

A rhoptry is a specialized secretory organelle. They are club-shaped organelles connected by thin necks to the extreme apical pole of the parasite. These organelles, like micronemes, are characteristic of the motile stages of Apicomplexa protozoans. They can vary in number and shape and contain numerous enzymes that are released during the process of host penetration. The proteins they contain are important in the interaction between the host and the parasite, including the formation of the parasitophorous vacuole (PV).

Besnoitia bennetti is a parasite that can cause besnoitiosis infections in donkeys. The range of this organism ranges from Africa to the United States. B. bennettii shares similar characteristics with Toxoplasma, Neospora, and Sarcocystis genera. Lab work onB. bennetti is conducted at biosafety level 1.

Besnoitia besnoiti is an apicomplexan protozoan parasite, closely related to Toxoplasma gondii and Neospora caninum,. It is part of a larger genus Besnoiti affecting multiple animal species, but Besnoita besnoiti, can affect livestock. and more specifically cattle as intermediate host, although some specific antibodies have been found in roe deer and red deer.

<i>Sarcocystis</i> Genus of protists in the apicomplex phylum

Sarcocystis is a genus of protozoan parasites, with many species infecting mammals, reptiles and birds. Its name is dervived from Greek sarx = flesh and kystis = bladder.

<i>Neospora</i> Genus of single-celled organisms

Neospora is a single celled parasite of livestock and companion animals. It was not discovered until 1984 in Norway, where it was found in dogs. Neosporosis, the disease that affects cattle and companion animals, has a worldwide distribution. Neosporosis causes abortions in cattle and paralysis in companion animals. It is highly transmissible and some herds can have up to a 90% prevalence. Up to 33% of pregnancies can result in aborted fetuses on one dairy farm. In many countries this organism is the main cause of abortion in cattle. Neosporosis is now considered as a major cause of abortion in cattle worldwide. Many reliable diagnostic tests are commercially available. Neospora caninum does not appear to be infectious to humans. In dogs, Neospora caninum can cause neurological signs, especially in congenitally infected puppies, where it can form cysts in the central nervous system.

<span class="mw-page-title-main">Equine protozoal myeloencephalitis</span> Central nervous system disease of horses

Equine protozoal myeloencephalitis (EPM) is a disease that affects the central nervous system of horses. It is caused by a protozoal infection that is brought about by the apicomplexan parasites Sarcocystis neurona or Neospora hughesi. Most cases are caused by S. neurona. The lifecycle and transmission of N. hughesi is not well understood. The parasites create lesions in both the brain and spinal cord of the affected horses leading to neurological issues. Most horses infected with S. neurona do not exhibit neurological symptoms consistent with EPM.

<span class="mw-page-title-main">Sarcocystidae</span> Family of single-celled organisms

The Sarcocystidae are a family of Apicomplexa associated with a variety of diseases in humans and other animals.

An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including Toxoplasma gondii, and Plasmodium falciparum and other Plasmodium spp., but not in others such as Cryptosporidium. It originated from algae through secondary endosymbiosis; there is debate as to whether this was a green or red alga. The apicoplast is surrounded by four membranes within the outermost part of the endomembrane system. The apicoplast hosts important metabolic pathways like fatty acid synthesis, isoprenoid precursor synthesis and parts of the heme biosynthetic pathway.

<span class="mw-page-title-main">Eucoccidiorida</span> Order of microscopic, spore-forming, single-celled parasites in the apicomplex phylum

The Eucoccidiorida are an order of microscopic, spore-forming, single-celled parasites belonging to the apicomplexan class Conoidasida. Protozoans of this order include parasites of humans, and both domesticated and wild animals including birds. Among these parasites are the Toxoplasma gondii that cause toxoplasmosis and Isospora belli, which results in isosporiasis.

<span class="mw-page-title-main">Ponazuril</span> Chemical compound

Ponazuril (INN), sold by Merial, Inc., now part of Boehringer Ingelheim, under the trade name Marquis® , is a drug currently approved for the treatment of equine protozoal myeloencephalitis (EPM) in horses, caused by coccidia Sarcocystis neurona. Veterinarians have been preparing a formulary version of the medication for use in small animals such as cats, dogs, and rabbits against coccidia as an intestinal parasite. Coccidia treatment in small animals is far shorter than treatment for EPM.

Chromera velia, also known as a "chromerid", is a unicellular photosynthetic organism in the superphylum Alveolata. It is of interest in the study of apicomplexan parasites, specifically their evolution and accordingly, their unique vulnerabilities to drugs.

<span class="mw-page-title-main">Apicomplexan life cycle</span> Apicomplexa life cycle

Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is typified by a cellular variety with a distinct morphology and biochemistry.

Hammondia hammondi is a species of obligate heteroxenous parasitic alveolates of domestic cats. Intracellular cysts develop mainly in striated muscle. After the ingestion of cysts by cats, a multiplicative cycle precedes the development of gametocytes in the epithelium of the small intestine. Oocyst shedding persists for 10 to 28 days followed by immunity. Cysts in skeletal muscle measure between 100 and 340 μm in length and 40 and 95 μm in width. Some of the intermediate hosts develop low levels of antibody and some cross-immunity against Toxoplasma.

Sarcocystis calchasi is an apicomplexan parasite. It has been identified to be the cause of Pigeon protozoal encephalitis (PPE) in the intermediate hosts, domestic pigeons. PPE is a central-nervous disease of domestic pigeons. Initially there have been reports of this parasite in Germany, with an outbreak in 2008 and in 2011 in the United States. Sarcocystis calchasi is transmitted by the definitive host Accipter hawks.

<i>Sarcocystis neurona</i> Species of protist

Sarcocystis neurona is primarily a neural parasite of horses and its management is of concern in veterinary medicine. The protozoan Sarcocystis neurona is a protozoan of single celled character and belongs to the family Sarcocystidae, in a group called coccidia. The protozoan, S. neurona, is a member of the genus Sarcocystis, and is most commonly associated with equine protozoal myeloencephalitis (EPM). The protozoan, S. neurona, can be easily cultivated and genetically manipulated, hence its common use as a model to study numerous aspects of cell biology.

<span class="mw-page-title-main">Jitender P. Dubey</span> Parasitologist and Microbiologist

Jitender P. Dubey is a veterinary parasitologist and microbiologist who pioneered the control and diagnosis of Toxoplasma gondii, Neospora caninum, and Sarcocystis neurona. Dubey discovered the life cycle of Toxoplasma gondii, and discovered and named both Neospora caninum and Sarcocystis neurona.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 Marsh, A.E.; Barr, B.C.; Packham, A.E; Conrad, P.A. (1998), "Description of a New Neospora Species (Protozoa: Apicomplexa: Sarcocystidae)", The Journal of Parasitology , 84 (5): 983–991, doi:10.2307/3284632, JSTOR   3284632, PMID   9794642
  2. 1 2 3 4 "EPM: Understanding This Debilitating Disease", American Association of Equine Practitioners, 2021
  3. ↑ McCoy, Annette; Firshman, Anna, "Equine Protozoal Myeloencephalitis (EPM)", University of Minnesota
  4. 1 2 3 4 5 6 Dubey, J.P. (2022), "Sarcocystis neurona, Neospora spp. and Toxoplasma gondii infections in horses and equine protozoal myeloencephalitis (EPM): five decades of personal experience, perspectives and update.", Parasitology, 149 (6): 717–728, doi:10.1017/S0031182021002055, PMID   35260209
  5. ↑ Lyons, E.T. (2015), "Etymology of the Scientific Names of Some Endoparasites in Horses" (PDF), University of Kentucky Agriculture
  6. ↑ Bjerkås, I.; Dubey, J.P. (1991), "Evidence that Neospora caninum is identical to the Toxoplasma-like parasite of Norwegian dogs", Acta Veterinaria Scandinavica, 32 (3): 407–410, doi: 10.1186/BF03546972 , PMC   8127930 , PMID   1814191
  7. 1 2 Holmdahl, J.; Björkman, C.; Stenlund, S.; Uggla, A.; Dubey, J.P. (1997), "Bovine Neospora and Neospora caninum: One and the same", Parasitology Today, 13 (1): 40–41, doi:10.1016/s0169-4758(97)81616-x, PMID   15275170
  8. 1 2 3 4 5 Learn About Parasites (2021), "Neospora caninum.", Western College of Veterinary Medicine
  9. 1 2 3 4 Fleige (2010), "Apicoplast: keep it or leave it", Microbes and Infection, 12 (4): 253–262, doi:10.1016/j.micinf.2009.12.010, PMID   20083219
  10. 1 2 Silva, R.C.; Machado, G.P. (2016), "Canine neosporosis: perspectives on pathogenesis and management", Veterinary Medicine: Research and Reports, 7: 59–70, doi: 10.2147/VMRR.S76969 , PMC   6055790 , PMID   30050838
  11. ↑ El Bakkouri, M (2013), "Structural Insights into the Inactive Subunit of the Apicoplast-localized Caseinolytic Protease Complex of Plasmodium falciparum", Journal of Biological Chemistry, 288 (2): 1022–1031, doi: 10.1074/jbc.m112.416560 , PMC   3542988 , PMID   23192353
  12. 1 2 3 Verhoef, JMJ; Meissner, M (2016), "Organelle Dynamics in Apicomplexan Parasites", mBio, 12 (4): e0140921, doi:10.1128/mbio.01409-21, PMC   8406264 , PMID   34425697
  13. 1 2 3 4 Wobeser, B.K.; Godson, D.L. (2009), "Equine protozoal myeloencephalitis caused by Neospora hughesi in an adult horse in Saskatchewan", The Canadian Veterinary Journal, 50 (8): 851–853, PMC   2711471 , PMID   19881924
  14. ↑ Henker, L.C.; Bandinelli, M.B. (2020), "Pathological, immunohistochemical, and molecular findings of equine protozoal myeloencephalitis due to Sarcocystis neurona infection in Brazilian horses", Tropical Animal Health and Production, 52 (6): 3809–3817, doi:10.1007/s11250-020-02419-y, PMID   33011934
  15. ↑ Goehring, L.S.; Sloet van Oldruitenborgh-Oosterbaan, M.M. (2001), "Equine protozoal myeloencephalitis (EPM) in Netherland [Equine protozoal myeloencephalitis in the Netherlands An overview]", Tijdschrift voor Diergeneeskunde, 126 (10): 346–351, PMID   11392988
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