Encephalitozoon cuniculi (früher auch als Nosema cuniculi bezeichnet) ist ein obligat intrazellulär in Niere, Gehirn und anderen Organen lebender parasitischer Einzeller. Er wird den Mikrosporidien zugerechnet, die genaue systematische Stellung dieses Parasiten ist jedoch noch nicht endgültig geklärt. Er ist der Erreger der Encephalitozoonose, einer vor allem bei Kaninchen, Altweltmäusen und Hundeartigen auftretenden Erkrankung, die auch auf Menschen mit einer Immunschwäche übertragbar ist.
Das Genom von E. cuniculi ist 2.9 Mbp groß und ist auf 11 Chromosomen mit Größen zwischen 217 und 315 kbp verteilt. E. cuniculi wird heute in drei genetisch und serologisch unterscheidbare Stämme untergliedert. Morphologisch sind diese drei Varianten nicht unterscheidbar. Sie werden als Typ I bis III oder nach ihrem jeweiligen Hauptwirt benannt.[1]:
Encephalitozoon cuniculi stellt sich in histologischen Präparaten als etwa 2–2,5 × 0,8–1,2 µm großes, leicht gebogenes Stäbchen mit abgerundeten Enden dar. Dem Erreger fehlen einige Zellorganellen, wie z. B. Mitochondrien.
Außerhalb der Wirtszellen kommt der Erreger als infektiöses Dauerstadium in Form einer Spore vor. Die etwa 2 µm großen Sporen bestehen aus einer Außen- (Exospore) und einer dickeren, chitinreichen Innenschicht (Endospore).[3] Im Zellplasma der Spore (Sporoplasma) befindet sich ein spiralig aufgerollter Polfaden.
Die Infektion des Wirts erfolgt über Sporen. Encephalitozoon cuniculi besitzt einen nur bei Mikrosporidien auftretenden Infektionsmodus: Der Polfaden wird ausgestülpt, durchdringt die Zellmembran und injiziert das Sporoplasma in die Wirtszelle. Etwa 10-mal häufiger gelangt die Spore jedoch durch gewöhnliche Phagozytose in eine Fresszelle (Makrophage). Dann wird als Zeichen der Keimung der Spore erst innerhalb der Fresszelle der Polfaden ausgestülpt, was die Entwicklung der Phagosomen in Lysosomen und damit ihren Abbau verhindert.[4]
Im Zytoplasma der Wirtszelle kommt es zu einer mehrfachen ungeschlechtlichen Vermehrung (Merogonie) und schließlich zur Sporenbildung. Dabei können bis zu 100 Sporoblasten je Zelle auftreten. Die Art der Erregerausbreitung im Wirt ist noch nicht genau bekannt. Der Erreger befällt vor allem die Nieren und das Gehirn. Die Ausscheidung der infektiösen Sporen erfolgt über den Urin.
Die Sporen sind sehr umweltresistent. Bei 25 °C sind sie drei Wochen, bei 10 °C drei Monate infektiös. Bei 100 °C sind sie nach 5 Minuten inaktiviert. Zur Desinfektion eignen sich kochendes Wasser, 2%iges Lysol, 1%iges Formaldehyd oder 70%iger Alkohol.
Encephalitozoon cuniculi (früher auch als Nosema cuniculi bezeichnet) ist ein obligat intrazellulär in Niere, Gehirn und anderen Organen lebender parasitischer Einzeller. Er wird den Mikrosporidien zugerechnet, die genaue systematische Stellung dieses Parasiten ist jedoch noch nicht endgültig geklärt. Er ist der Erreger der Encephalitozoonose, einer vor allem bei Kaninchen, Altweltmäusen und Hundeartigen auftretenden Erkrankung, die auch auf Menschen mit einer Immunschwäche übertragbar ist.
Encephalitozoon cuniculi (E. cuniculi) is a mammalian microsporidial pathogen with world-wide distribution. An important cause of neurologic and renal disease in rabbits, E. cuniculi can also cause disease in immunocompromised people.
E. cuniculi is a spore-forming unicellular parasite belonging to the phylum Microsporidia. Microsporidia are obligate intracellular parasitic fungi infecting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution.
The genome consists of approximately 2.9-megabases (Mbs) in 11 chromosomes, with a total of 1,997 potential protein-coding genes.[1] Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues.[2] At the time of publication (2001), only 44% of the proteins had a function assigned to them. the latest reference proteome in Uniprot (2021) lists 2041 proteins with ~620 proteins annotated as "uncharacterized", about 200 without annotation (e.g. "UPF0329 protein ECU06_1620") and another ~150 or so that are annotated as having some "domain" (including domains of unknown function) and numerous proteins of "probable" and "putative" function plus dozens with "similarity" to characterized proteins.[3] Hence, even 20 years after the genome sequence was published, about 50% of the E. cuniculi proteome remains uncharacterized or poorly understood.
The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), it is possible that microsporidia have retained a mitochondrion-derived organelle.[2]
The infective form of microsporidia (E. cuniculi) is a resistant spore which can survive for a long time in the environment. The spore extrudes its polar tubule and infects the host cell. The spore injects the infective sporoplasm into the eukaryotic host cell through a polar tube. Inside the cell, the sporoplasm undergoes extensive multiplication. This multiplication occurs either by merogony (binary fission) or schizogony (multiple fission). Microsporidia develop by sporogony to mature spores in the cytoplasm or inside parasitophorous vacuole. During sporogony, a thick wall is formed around the spore. The thick wall formed provides resistance to adverse environmental conditions. Once the spores increase in number and completely fill the cytoplasm of the host's cell, the cell membrane is disrupted and releases the spores to the surroundings. These free mature spores can infect new cells thus continuing the cycle.
First identified in rabbits, E. cuniculi infections have been reported worldwide in over 20 mammalian species, including humans. Prevalence in pet rabbits is high, with 23–75% having antibodies to the disease. Studies of healthy dogs have found a 0–38% prevalence. Cats appear to be relatively resistant to the organism, although experimental infections in kittens with feline leukemia virus have been described. E. cuniculi also infects rodents, and the organism has been detected in the feces of 13% of pet birds. A small percentage of healthy people have antibodies to the organism, indicating previous exposure. Seroprevalence rates are higher in immunocompromised people, and in those who live in or have visited tropical countries. Most infections do not result in clinical disease.[4]
E. cuniculi spores are usually shed in urine, but can also be found in the feces and respiratory secretions of infected animals. Spores can be detected in urine 38 to 63 days after infection, with intermittent shedding thereafter. Ingestion of spores is the main route of transmission, although inhalation of spores can also occur. Transplacental and intrauterine infections have been documented in rabbits.[4]
Up to 80% of rabbits in the United States and Europe are serologically positive for E. cuniculi, which indicates that they have been exposed to the organism. Most of these animals will remain asymptomatic and never show signs of disease. Only a small minority of infected rabbits develop the disease encephalitozoonosis. The most common clinical signs associated with this disease involve the central nervous system, eyes, and kidneys.[5]
Most rabbits with neurologic signs show vestibular dysfunction only. Symptoms often appear suddenly, and include head tilt, ataxia, nystagmus, and circling. Most of these animals are still aware of their surroundings and are eating despite their loss of balance. More severely affected rabbits, such as those which can no longer stand, have a worse prognosis.[6]
E. cuniculi infections in the eye cause cataract formation, white intraocular masses, and uveitis. Symptoms usually occur in young rabbits, and only one eye is generally affected. Rabbits with ocular lesions related to encephalitozoonosis are usually otherwise healthy, and tolerate vision loss well.[6]
E. cuniculi has a predilection for the kidneys and can cause chronic or acute kidney failure. Symptoms of renal impairment include increased water consumption, increased urine output, loss of appetite, weight loss, lethargy, and dehydration. Milder cases do not cause symptoms, and signs of infection may be an incidental finding on necropsy.[6]
It is currently difficult to definitively diagnose E. cuniculi infections in live rabbits. A presumptive diagnosis is often made based on consistent clinical signs and high antibody levels. Serology tests that look for IgG antibodies are commonly run, and can be used to rule out the disease if negative. However, a positive IgG titer cannot differentiate an active infection from a previous infection or an asymptomatic carrier state.[7] Tests for IgM antibodies are also available, but again positive results cannot distinguish between active and latent infections.[6]
Polymerase chain reaction (PCR) has long been established as the standard technique for detection of microsporidia in humans, and attempts to apply this to rabbits are ongoing. Studies have found that PCR of liquified lens material is a reliable means of diagnosing E. cuniculi uveitis in rabbits, but PCR testing of rabbit urine and cerebrospinal fluid is not reliable.[6]
A few studies have shown that albendazole, a benzimidazole drug, can prevent and treat naturally acquired and experimentally induced E. cuniculi infections. Unfortunately the elimination of spores from the central nervous system does not always result in resolution of clinical signs. Adverse reactions to benzimidazole drugs, including injury to the small intestine and bone marrow, have been reported in rabbits. Practitioners should strictly adhere to recommended dosages and treatment intervals, and consider monitoring complete blood counts during treatment.[6]
E. cuniculi is an important opportunistic pathogen in people, particularly those immunocompromised by HIV/AIDS, organ transplantation, or CD4+ T-lymphocyte deficiency. As this organism is more common in animals than people it is likely a zoonotic disease. Three different strains of E. cuniculi have been identified, and are classified as I (rabbit), II (mouse), and III (dog).[4] Human-to-human transmission is possible via transplantation of solid organs from an infected donor.[8]
Encephalitozoon cuniculi (E. cuniculi) is a mammalian microsporidial pathogen with world-wide distribution. An important cause of neurologic and renal disease in rabbits, E. cuniculi can also cause disease in immunocompromised people.
Encephalitozoon cuniculi est une microsporidie parasite intracellulaire d’autres eucaryotes.
Encephalitozoon cuniculi fut la 1re infection de mammifère observée chez le lapin en 1922. Il peut infecter les lapins, les souris et les rats de laboratoire. Le parasite provoque des granulomes cérébraux et cause des infections chroniques du lapin. Cette infection pose problème dans les animaleries de laboratoires mais surtout dans les élevages de lapins. La prévalence d’Encephalitozoon cuniculi chez les lapins sauvages est inférieure à 25 %, alors qu’elle est de 76 % pour les lapins de laboratoire.
Chez l’homme, le 1er cas a été décrit en 1959. Il concernait un garçon de 9 ans présentant des maux de tête, de la fièvre et des convulsions. Les cas d’infection étaient assez rares, mais une forte augmentation est observée depuis le milieu des années 1970 avec l’augmentation du nombre d’immunodéprimés (greffe, VIH…).
Ce parasite peut entraîner des hépatites et des conjonctivites, il est dangereux notamment pour les personnes immunodéprimées.
Récemment une infection du cerveau a été constatée chez l’homme. À la suite de ces observations, l’institut national des maladies allergiques et infectieuses des États-Unis a classé Encephalitozoon cuniculi comme agent infectieux émergent.[Quand ?]
Le diagnostic peut se faire grâce à des techniques sérologiques (test ELISA) ou par examen histologique ; une technique de PCR a aussi été développée pour le diagnostic de ce parasite.
Pour le traitement, il existe différentes molécules plus ou moins efficaces, notamment l'albendazole, utilisé lors des infections chez les personnes séropositives. Certains corticoïdes peuvent aussi être utilisés.
Le génome d'Encephalitozoon cuniculi a été entièrement séquencé[1]. Il est très compact avec 2,9 Mbases (l’un des génomes eucaryotes les plus petits connus à ce jour). Le génome comporte 2000 gènes organisés sur 11 chromosomes. Les gènes sont très proches les uns des autres. On constate très peu de séquences répétées et non codantes dans l’ADN (seulement 11 introns) et quelques séquences intergéniques flanquantes (donc pas d’ORF chevauchant) ce qui suggère qu'Encephalitozoon cuniculi pourrait coder l’information dont il a besoin de manière très efficace et ceci montre une parfaite adaptation au parasitisme. Les gènes impliqués dans le cycle de Krebs et la chaîne respiratoire sont manquants. Il y a peu de gènes impliqués dans la biosynthèse des acides aminés. Il existe plusieurs délétions dans les gènes codant les ARN ribosomiques.
Encephalitozoon cuniculi est une microsporidie parasite intracellulaire d’autres eucaryotes.
