Naegleria

Naegleria

Page updated 25/4/03

A very common genus of soil and freshwater amoebo-flagellate from the Vahlkampfiid family. The genus Naegleria has a long history. It was named by Alexeieff (Alexeieff, 1912), was formerly known as Dimastigamoeba, as its members typically have two flagella, but was originally described as Amoeba gruberi (Schardinger, 1899). Three stages exist the amoeba, the bi-flagellate and the cyst. Much is known about this genus (Marciano-Cabral, 1988) because of its abundance, the problems it can cause in human health, and because it has been used as a model for eukaryotic differentiation. Much remains to be discovered about its biology however, and its mysteries are compounded by its position as a very early branching eukaryote. Naegleria has been the subject of a recent excellent review that concentrates on the classification and pathogenicity of the genus (De Jonckheere, 2002).

Figure 1. This Naegleria has been compressed under a coverslip to envisage internal detail. Phase contrast microscopy. Note the centrally located phase dense nucleolus (n). The morphology of the amoebae is usually cylindrical with a contractile rear apparently squeezing cytoplasm forwards in locomotion. (See Locomotion of Naegleria)

This photomicrograph is of Naegleria pringsheimi (previously known as N. gruberi CCAP 1518/1c) now supplied by ATCC 30875

Figure 2. An early Naegleria gruberi (NEG-M) flagellate, note that the nucleus is positioned closely with the flagellar root. The entire flagellar structure requires the synthesis of some 200 proteins. This remarkable transformation takes place within 100 minutes from initiation. The laboratory of Chandler Fulton has been using Naegleria transformation as a model system for differentiation. (Hoffman optics, magnification same as Figure1).

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Pathogenicity of Naegleria
A few Naegleria species have been shown to be pathogenic in humans and animals most notably N. fowleri. This amoeba is a facultative pathogen capable of living many generations without infecting a host. Trophozoites are thought to enter the nose during swimming in warm water and thereafter the brain by locomotion and destruction of neurons. N. fowleri causes Primary Amoebic Meningoencephalitis (PAM) in man Naegleria fowleri posesses secreted proteases (Ferrante & Bates, 1988), phospholipases (Fulford et al, 1985; Barbour & Marciano-Cabral, 2001), and pore-forming peptides (Herbst et al, 2002), all of which have been implicated in the pathogenic process. Although man can act as a host, this occurs so infrequently that we are very unlikely to be the primary host. This host (if indeed there is one) has not yet been clearly identified, but many any other mammals have been reported to be infected or infectable. These include; mice, cotton rats, squirrels, muskrats (John & Hope, 1990), guinea pigs (Culbertson et al, 1972), and sheep (Young et al, 1980). Many wild animals (but not all) have significant titres of Naegleria reactive antibodies suggesting that they come into contact with this group (Kollars & Wilhelm, 1996). It is possible that the main host are fish as these are frequently found to be parasitized by Naegleria and other amoebae (especially the gills). Invertebrates too cannot be ruled out as snails, amphibians and reptiles are also associated with Naegleria (Franke & Mackiewicz, 1982).

As in other amoebae there is a strong correlation between temperature tolerance and pathogenicity of Naegleria species (Griffin, 1972). Naturally, any amoeba that lives within a human host must be able to survive the normal 37^oC and elevation above this that occurs in disease associated fevers. The majority of human PAM cases are caused by Naegleria fowleri which can grow at temperatures as high as 45^oC. N. fowleri and other temperature tolerant Naegleria sp. multiply in bodies of water both natural and man-made that are warm and most PAM cases where Naegleria is involved have been caused by swimming or other intimate contact with warm waters (De Jonckheere & Van de Voorde, 1977). However there have been at least three cases have been documented where no association with water has been made (Lawande et al, 1979; Sugita et al, 1999; Shenoy et al, 2002). Naegleria is thought to enter the body through the nose and both pathogenic and non-pathogenic Naegleria has been isolated from the nasal mucosa of non-infected individuals (Cerva et al, 1973; el-Marhoumy et al, 1988).

Pathogenic Naegleria in the U.K.

The Interaction of pathogenic Naegleria with host cells.
Both pathogenic (Chi et al, 1959) and non-pathogenic (Alonso & Zubiaur, 1985) Naegleria phagocytose red blood cells and tissue cultured cells (Cursons & Brown, 1978). The aggressive phagocytosis seen by Naegleria is accomplished by a specialised feeding apparatus called the "amoebostome", an actin-rich sucker

Treatment of Primary Amoebic Meningoencephalitis (PAM)
Of the 300 or so cases of this disease world-wide, only seven or so have been survived (Jain et al, 2002). The drug of choice has been amphotericin B (Anderson & Jamieson, 1972;Seidel et al, 1982;Jain et al, 2002 ) it is usually given intravenously at 1mg/kg/day (see Shenoy et al, 2002). In the cases where patients have survived early diagnosis has been crucial. Symptoms are generally like bacterial meningitis but with no bacteria in the cerebrospinal fluid, the presence of amoebae can however be detected by observation of the CSF under a microscope. The incubation period is usually between 3 and 8 days and the patient usually dies 7-10 days after infection (Butt, 1966; Anderson & Jamieson, 1972; Barnett et al, 1996).

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Molecular Biology of Naegleria

The nucleus of Naegleria is similar in overall structure to a number of protists in that the nucleolus is very prominent (Figure 1).

Although the ploidy (how many copies of the genome exist in the nucleus) of Naegleria is not known it is suspected that it is polyploid (Clarke et al, 1990). There are about 23 chromosomes with total genome of about 104 Mb (Clarke et al, 1990). The most remarkable thing about the molecular biology of Naegleria is that the rRNA genes are carried on a 14 Kb plasmid present as a multi-copy (4,000) episome! (Clark & Cross, 1987). These circular plasmids are a feature of the Vahlkampfiid amoeba (Clark & Cross, 1988) and are easily isolated from the amoeba (click here for method).

External Naegleria Links:-

Naegleria gruberi mitochondrial genome.

David Caprette -Rice University on Naegleria transformation

Charles Walsh - University of Pittsburgh Naegleria page

Francine Marciano-Cabral - Medical College of Virginia

CDC Atlanta Georgia

Simon Kilvington- University of Leicester

Classification of Naegleria species

Many different strains of Naegleria have been isolated and most described as belonging to the N. gruberi groups, however molecular analysis indicates that these are not monophylectic and the genus has now been reclassified into some 24 species (this number will soon expand). In order to simplify the classification, only the current situation will be discussed based on molecular data (usually 5.8S rDNA or SSUrDNA gene data). See (De Jonckheere 2002) for details.

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Described strains (and availability):-

N. australiensis (De Jonckheere, 1981) related to N. tihangensis.

N. andersoni (De Jonckheere, 1988) related to N. jamiesoni.

N. carteri (Dobson et al, 1997) No strain available at ATCC or CCAP.

N. clarki (De Jonckheere, 1984) ATCC 30544 sewage effluent, Ohio, 1969

N. chilensis (De Jonckheere et al, 2001). related to N.pussardi.No known flagellar stage

N. fowleri (Carter, 1970)

N. fultoni (De Jonckheere et al, 2001) related to N. pringsheimi.

N. galeacystis (De Jonckheere, 1994a)

N. gruberi (Schardinger, 1899)

N. indonesiensis (De Jonckheere et al, 2001) No known flagellar stage

N. italica (De Jonckheere et al, 1984)

N. jadini (Willaert & Le Ray, 1973)

N. jamiesoni (De Jonckheere, 1988)

N. lovaniensis (Stevens et al, 1980) ATCC 30467 domestic water supply, Kadina, Australia, 1972.
ATCC30569 Bowling Green, OH, 1970.

N. minor (De Jonckheere & Brown 1995) Flagellar stage has four flagella and can divide but only once.

N. morganensis (Dobson et al, 1997)

N. niuginesis (Dobson et al, 1997) No strain available at ATCC or CCAP.

N. pagei (De Jonckheere, 2002)

N. philippinensis (De Jonckheere, 2002)

N. pringsheimi (De Jonckheere, 2002)

N. pussardi (Pernin & De Jonckheere, 1996)

N. robinsoni (De Jonckheere & Brown, 1999) Type strain NG944 CCAP 1518/19; Flagellar stage has four flagella and can divide but only once to produce a bi-flagellated cell. This is the same situation as N. minor but there is no relationship by SSUrDNA gene sequence. N.robinsoni is related to N.indonesiensis.

N. sturti (Dobson et al, 1997)

N. tihangensis (De Jonckheere, 2002)

Parasites of Naegleria

Bacteria.
Many amoebae are known to harbour bacteria both free in the cytoplasm and contained within vacuoles. Some bacteria such as those found in Amoeba proteus, and Pelomyxa palustris are commensal and as such appear to be mutually beneficial. A strain of Naegleria however has been found to contain an intracellular gram-negative bacteria known as "KNic" (Michel et al, 2000). This bacteria inhibits the ability to form cysts but not flagellates, presumably a clever ploy to prevent the amoeba from shutting its self down and so to prevent the spread of the bacteria to surrounding Naegleria sp while permitting formation of the flagellate stage which would help the bacteria spread? Were this to be the case one would expect KNic also to inhibit apoptosis (if this occurs in Naegleria?). KNic is an odd looking bacteria, looking like a golf ball by SEM and miniature Acanthamoeba cysts in cross section TEM (Michel et al, 2000). The KNic bacteria could not be cultured on the many media tried but was found to infect a number of other amoebae (Hartmannella, Vahlkampfia, Balamuthia and even Dictyostelium). KNic was surrounded by an electron translucent region, however no membrane could be seen indicating that the bacteria were free in the amoebal cytoplasm (Michel et al, 2000) presumably bound by some sort of bacterially produced polymer?

Viruses.
Less is known about viral infections in the genus Naegleria. Virus-like particles have described in several strains, and a bacteriophage has been dicovered in association with an obligate bacteria that looks like the KNic bacteria (Michel et al, 2001). This phage is named "Neo-Ph/2" due to its similarity to a phage from a bacteria Neochlamydia hartmannellae that infects the amoeba Hartmannella vermiformis (Schmid et al, 2001).

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Relationships to other Heterobosea

References:-

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