Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Naegleria fowleri”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Eating the brain - A multidisciplinary study provides new insights into the mechanisms underlying the cytopathogenicity of Naegleria fowleri.

Naegleria fowleri, the causative agent of primary amoebic meningoencephalitis (PAM), requires increased research attention due to its high lethality and the potential for increased incidence as a result of global warming. The aim of this study was to investigate the interactions between N. fowleri and host cells in order to elucidate the mechanisms underlying the pathogenicity of this amoeba. A co-culture system comprising human fibrosarcoma cells was established to study both contact-dependent and contact-independent cytopathogenicity. Proteomic analyses of the amoebas exposed to human cell cultures or passaged through mouse brain were used to identify novel virulence factors. Our results indicate that actin dynamics, regulated by Arp2/3 and Src kinase, play a considerable role in ingestion of host cells by amoebae. We have identified three promising candidate virulence factors, namely lysozyme, cystatin and hemerythrin, which may be critical in facilitating N. fowleri evasion of host defenses, migration to the brain and induction of a lethal infection. Long-term co-culture secretome analysis revealed an increase in protease secretion, which enhances N. fowleri cytopathogenicity. Raman microspectroscopy revealed significant metabolic differences between axenic and brain-isolated amoebae, particularly in lipid storage and utilization. Taken together, our findings provide important new insights into the pathogenic mechanisms of N. fowleri and highlight potential targets for therapeutic intervention against PAM.

Naegleria fowleri↗
PubMed1979

Differences in virulence of Naegleria fowleri.

All pathogenic Naegleria fowleri isolated from the environment were highly virulent to mice when instilled intranasally. Axenic cultivation gradually decreased virulence of highly virulent strains. This decrease was most pronounced in environmental isolates and of minor importance in N. fowleri isolated from human cerebrospinal fluid. The low virulent strains obtained by continuous axenic cultivation appeared after clonation to consist of individuals with different virulence. Virulence could be enhanced in low virulent strains by brain passage and passages in Vero cell cultures, but could not be induced by these methods in nonvirulent strains isolated from the environment. Different mice strains showed different sensitivities to infection with pathogenic Naegleria. In addition, older mice were less sensitive than younger animals to low virulent strains.

Aging↗
PubMed2025

Detection and identification of Naegleria species along with Naegleria fowleri in the tap water samples.

Naegleria fowleri, the causative agent of Primary Amoebic Meningoencephalitis (PAM), is commonly found in warm freshwater environments and can enter the brain through nasal passages during activities like swimming or ablution. PAM has a high fatality rate, raising concerns about its global health impact. In Pakistan, particularly in Karachi, a significant number of cases have been reported, often with no history of recreational water exposure, but with regular ablution using tap water. This study analyzed the physicochemical parameters, abundance of total and fecal coliforms, and detected N. fowleri and other Naegleria species in tap water samples from Karachi using PCR with ITS- and Naegl-primers. Almost all samples exhibited high temperatures, low chlorine levels, and a high presence of coliforms. N. fowleri and other Naegleria species were detected in 11 out of 39 samples. Sequence analysis identified N. fowleri in tap water from the Golimar and Lyari areas of Karachi, while the other nine samples revealed different Naegleria species. This study suggests that the combination of high temperatures, insufficient chlorination, and the presence of coliforms may create favorable conditions for N. fowleri growth. However, these factors are not exclusive to the Golimar and Lyari areas, indicating that other environmental or infrastructural factors, not detailed in this study, may have contributed to the presence of N. fowleri in that specific location.

Naegleria fowleri↗
PubMed1978

Protective immunity to Naegleria fowleri in experimental amebic meningoencephalitis.

Naegleria fowleri, a free-living ameboflagellate, is the causative organism of primary amebic meningoencephalitis. Intranasal inoculation of N. fowleri in mice produces an infection similar to human disease. Mice immunized with live N. fowleri by intraperitoneal injection were found to be more resistant to subsequent intranasal challenge. These results may provide a lead to the development of immunotherapy for this virulent disease for which satisfactory chemotherapy is presently unavailable.

Amebiasis↗
PubMed1978

Observations by light microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

Naegleria fowleri, strain HB-1, caused a destructive cytopathic effect (CPE) in secondary mouse-embryo (ME) cells. No evidence was found to suggest that cell-free cytotoxic factors secreted by the amoebae play a part in ME-cell destruction. In culture systems designed for the study of cytopathic factors, mammalian-cell damage seemed to occur only as a result of direct contact with active amoebae. This was confirmed when the progressive destruction of individual ME cells was observed continuously by direct microscopy and time-lapse cinemicrography. The cytoplasmic shrinkage characteristic of naegleria-induced CPE appeared to be associated with phagocytic activity of trophozoites. Adjacent ME cells remained undamaged until they themselves were physically attacked. The apparently intracellular location of amoebae seen in fixed and stained preparations was considered to be an artefact created when trophozoites and ME cells were superimposed.

Amoeba↗
PubMed1979

Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol.

Growth of the pathogenic amoeboflagellate Naegleria fowleri is inhibited by delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment, but does not impair amoeboid movement. Calf serum at 10 and 20% (vol/vol) reduces the antiamoeba activity of delta 9-THC. Only 1-methoxy delta 8-tetrahydrocannabinol, of 17 cannabinoids tested, failed to inhibit growth of N. fowleri. Antinaeglerial activity was not markedly altered by opening the pyran ring, by converting the cyclohexyl ring to an aromatic ring, or by reversing the hydroxyl and pentyl groups on the benzene ring. delta 9-THC prevented the cytopathic effect of N. fowleri on African green monkey (Vero) cells and human epithelioma (HEp-2) cells in culture. delta 9-THC afforded modest protection to mice infected with N. fowleri.

Amebiasis↗
PubMed1978

Innate resistance of mice to experimental infection with Naegleria fowleri.

The mouse system provides an excellent model for studying host resistance to Naegleria fowleri, the agent of primary amoebic meningoencephalitis. Innate resistance to infection with N. fowleri was examined with respect to infecting dose and the age, sex, and strain of mice. Intravenous inoculation with 10(7) amoebae per mouse produced 100% mortality in 9 days, whereas inoculation with fewer amoebae reduced the cumulative mortality. Male and female DUB/ICR mice of varying ages were inoculated intravenously with 2.5 X 10(5) N. fowleri per g of body weight. The youngest mice died first, with 100% mortality for both males and females, and mortality decreased with increasing age. Female mice were significantly more resistant to infection than males. Five strains of mice weighing approximately 20 g were inoculated intravenously with weight-adjusted doses; mortality ranged from 10% in C57BL/6 mice to 95% in A/HeCr mice.

Age Factors↗
PubMed1979

Observations by immunofluorescence microscopy and electron microscopy on the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

The destruction of secondary mouse-embryo (ME) cells by Naegleria fowleri was studied by indirect immunofluorescence with ME-cell antiserum as a specific label to trace the fate of mammalian-cell cytoplasm. The appearance of naegleria-induced cytopathic effect in the cultures coincided with the accumulation of discrete particles containing granules of ME-cell antigen within the cytoplasm of amoebae, suggesting that the organisms ingested host-cell material. In cultures containing cytochalasin B, a non-lethal inhibitor of phagocytosis by N. fowleri trophozoites failed to acquire any granular fluorescence and were not cytopathogenic. The engulfment of mammalian-cell cytoplasm by the organisms was confirmed when thin sections of naegleria-infected ME-cell cultures were examined by electron microscopy. Amoebae were seen in the process of detaching portions of cytoplasm from whole ME cells by means of distinctive ingesting pseudopodia, and fragments of mammalian-cell cytoplasm were identified within the food vacuoles of trophozoites. There was no evidence for cytotoxic disruption of ME cells before or during engulfment of these fragments. It is concluded that N. fowleri trophozoites attack and destroy cultured ME cells by a phagocytosis-like mechanism alone, without the aid of any amoeba-associated cytotoxic or cytolytic agents. The possible significance of these findings with respect to the in-vivo pathocity of N. fowleri is discussed.

Amoeba↗
PubMed1979

Inhibition by amoeba-specific antiserum and by cytochalasin B of the cytopathogenicity of Naegleria fowleri in mouse embryo-cell cultures.

Inhibitors of trophozoite motility and phagocytosis were used to investigate the mechanism of Naegleria fowleri cytopathogenicity in mouse-embryo (ME)-cell cultures. Amoebae that were immobilised and agglutinated by specific antiserum exhibited no cytopathic activity, although they remained alive and were in constant contact with the ME cells. Mammalian-cell damage occurred only when the organisms recovered pseudopodium function and began to migrate over the monolayers as they overcame the inhibitory effects of the antiserum. Cytochalasin B at a concentration of 10 microgram/ml, shown to prevent the engulfment of chick erythrocytes by amoebae, also inhibited the cytopathogenicity of Naegleria when incorporated in ME-cell culture medium. Despite repeated contact with active trophozoites, the ME cells showed only those morphological changes characteristically induced by cytochalasin B itself. The amoebae in turn showed signs of starvation after 3 or 4 days' incubation, suggesting that the feeding activity of trophozoites was suppressed. Colchicine, on the other hand, inhibited neither the ingestion of erythrocytes nor the destruction of ME cells by amoebae. It was concluded that the cytopathogenicity of N. fowleri in ME-cell cultures was due to physical rather than biochemical or cytotoxic mechanisms and was associated with the phagocytic activity of trophozoites.

Amoeba↗
PubMed1975

Experimental infections with pathogenic free-living amebae in laboratory primate hosts: I (A) A study on susceptibility to Naegleria fowleri.

Studies were conducted on 27 Old World monkeys to determine their susceptibility to pathogenic strains (HB-1 and C-66) of Naegleria fowleri by intranasal, intravenous, or intrathecal inoculation of trophozoites. No clinically detectable disease resulted from either intranasal or intravenous inoculation, but 11 of 18 monkeys inoculated intrathecally succumed to acutely fatal meningoencephalitis, while the other 7 survived with no obvious permanent brain damage. Pathogenicity of N. fowleri appeared to be influenced by the strain virulence, growth phase, and cultural condition of the amebae, as well as age, immune competence, and other as yet unknown host factors.

Administration, Intranasal↗
PubMed1979

Naegleria fowleri in chick embryos. Effects of embryo age and incubation temperature, and the infectivity of embryo-derived amebae for mice.

Chick embryos were infected with Naegleria fowleri which was initially isolated from an ultimately fatal human case. Following inoculation of equivalent numbers of amebae on the chorioallantoic membrane, younger embryos died earlier than older embryos infected at the same time. Incubation of infected embryos at 32 degrees C prolonged survival only slightly in comparison with those at 37 degrees C. N. fowleri maintained for more than 25 serial passages in chick embryos retained infectivity for mice and the ability to convert to the biflagellate form in vitro.

Age Factors↗
PubMed1978

Some further characteristics of the growth of Naegleria fowleri and N. gruberi in axenic culture.

The effects of pH, various viscosity of the medium, changed ratio between the concentrations of dissolved and corpuscular components in the medium, and dissolved inorganic salts on the growth of axenic cultures of Naegleria fowleri and N. gruberi have been studied. The cultures were grown in liquid CALYG and BCS media. The pH optimum was 6.5 for N. fowleri and 6.0--6.5 for N. gruberi. No negative influence on the growth of N. fowleri was observed even at 0.5% concentration of highly viscous methylcellulose, whereas the growth of N. gruberi was distinctly inhibited by more than 0.2% of methycellulose. N. fowleri preferred the osmotorphic and N. gruberi phagotrophic nutrition in the given system of cultivation. The growth of both Naegleria species was inhibited by 0.1 N concentration of sodium chloride and potassium chloride without any significant difference in the tolerance. The inhibitory effect of these salts correlated primarily with the concentration of chloride anion. The ability to grow in a medium with increased viscosity and the preference for osmotrophic nutrtion are, besides the higher temperature optimum determined earlier, further characteristics of the pathogenic species N. fowleri.

Amoeba↗
PubMed1979

In vitro susceptibilities of Naegleria fowleri strain HB-1 to selected antimicrobial agents, singly and in combination.

The overall prognosis of primary amoebic meningoencephalitis remains poor. The results of this study support previous finding that amphotericin B is the most efficacious drug against the Naegleria species in in vitro testing. In addition, the methyl ester of amphotericin B, a new derivative, also appears to be an effective agent. Of the drug combinations studied, amphotericin B plus minocycline and amphotericin B plus tetracycline showed synergy. The clinical significance of these findings remains to be determined.

Amoeba↗