Description of a <i>Naegleria</i> sp. isolated from two cases of primary amoebic meningo‐encephalitis, and of the experimental pathological changes induced by it

Carter, Rodney F.

doi:10.1002/path.1711000402

Cited by 236 publications

(144 citation statements)

References 32 publications

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“…Their diversity is likely to be high. In recent years, many new species have been discovered (28), including halophiles (46), thermophiles (47), and a single human pathogen, Naegleria fowleri, which causes primary amoebic meningoencephalitis, a nearly uniformly fatal disease of the central nervous system (48). Like other free-living amoebae, the heteroloboseans are phagotrophic protists and consume bacteria, including cyanobacteria (18).…”

Section: Discussionmentioning

confidence: 99%

Impairment of O-antigen production confers resistance to grazing in a model amoeba–cyanobacterium predator–prey system

Simkovsky

Daniels

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The grazing activity of predators on photosynthetic organisms is a major mechanism of mortality and population restructuring in natural environments. Grazing is also one of the primary difficulties in growing cyanobacteria and other microalgae in large, open ponds for the production of biofuels, as contaminants destroy valuable biomass and prevent stable, continuous production of biofuel crops. To address this problem, we have isolated a heterolobosean amoeba, HGG1, that grazes upon unicellular and filamentous freshwater cyanobacterial species. We have established a model predator–prey system using this amoeba and Synechococcus elongatus PCC 7942. Application of amoebae to a library of mutants of S. elongatus led to the identification of a grazer-resistant knockout mutant of the wzm ABC O-antigen transporter gene, SynPCC7942_1126. Mutations in three other genes involved in O-antigen synthesis and transport also prevented the expression of O-antigen and conferred resistance to HGG1. Complementation of these rough mutants returned O-antigen expression and susceptibility to amoebae. Rough mutants are easily identifiable by appearance, are capable of autoflocculation, and do not display growth defects under standard laboratory growth conditions, all of which are desired traits for a biofuel production strain. Thus, preventing the production of O-antigen is a pathway for producing resistance to grazing by certain amoebae.

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Section: Discussionmentioning

confidence: 99%

Impairment of O-antigen production confers resistance to grazing in a model amoeba–cyanobacterium predator–prey system

Simkovsky

Daniels

Tang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…These results confirmed previous experiments with BSM and PSM, and showed that the mucin MUC5AC may be an important protective barrier, reducing adhesion and cytotoxicity to the airway epithelium. Histopathological studies using a murine model have shown that this amoeba infects its host by invading the olfactory mucosa, migrating through the olfactory nerves, crossing the cribiform plate, and entering the olfactory bulbs (Carter, 1970;Jarolim et al, 2000Jarolim et al, , 2002. At the very early stages of infection, trophozoites are observed at the lumen of the nasal cavity embedded in mucus secretions (Rojas-Hernández et al, 2004).…”

Section: Nci-h292 Cells and Muc5ac Assaysmentioning

confidence: 99%

“…It has been demonstrated that this protozoan gains access to the CNS by penetrating the olfactory neuroepithelium and invading the olfactory bulbs (Carter, 1970;Jarolim et al, 2000Jarolim et al, , 2002Rojas-Hernández et al, 2004). Once in the CNS, the amoebae induce a strong inflammatory response with lysis of leukocytes that contributes to tissue damage (Cervantes-Sandoval et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

et al. 2008

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Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM). This parasite invades its host by penetrating the olfactory mucosa. During the initial stages of infection, the host response is initiated by the secretion of mucus that traps the trophozoites. Despite this response, some trophozoites are able to reach, adhere to and penetrate the epithelium. In the present work, we evaluated the effect of mucins on amoebic adherence and cytotoxicity to Madin-Darby canine kidney (MDCK) cells and the MUC5AC-inducing cell line NCI-H292. We showed that mucins inhibited the adhesion of amoebae to both cell lines; however, this inhibition was overcome in a time-dependent manner. N. fowleri re-established the capacity to adhere faster than N. gruberi. Moreover, mucins reduced the cytotoxicity to target cells and the progression of the illness in mice. In addition, we demonstrated mucinolytic activity in both Naegleria strains and identified a 37 kDa protein with mucinolytic activity. The activity of this protein was inhibited by cysteine protease inhibitors. Based on these results, we suggest that mucus, including its major mucin component, may act as an effective protective barrier that prevents most cases of PAM; however, when the number of amoebae is sufficient to overwhelm the innate immune response, the parasites may evade the mucus by degrading mucins via a proteolytic mechanism.

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“…fowleri is the causal agent of PAM, and the acquisition of this entity is commonly associated with a recent history of aquatic activity by the patient (Schuster & Visvesvara, 2004). The route of invasion of N. fowleri has been analysed by histopathological studies using a mouse model (Carter, 1970;Cervantes-Sandoval et al, 2008a;Jaroli et al, 2002). These studies revealed that the amoeba infects the host by first penetrating the olfactory mucosa and subsequently crossing the cribriform plate of the ethmoid bone, eventually reaching the olfactory bulbs of the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…PAM is an acute and rapidly fatal infection that is characterized by parasitic invasion of the central nervous system (CNS). The parasite gains access to the CNS by penetrating the olfactory neuroepithelium and migrating through olfactory nerves until it reaches the olfactory bulbs (Carter, 1970;Jaroli et al, 2002;Jarolim et al, 2000;Rojas-Hernández et al, 2004;Shibayama et al, 2003). Immunohistochemical studies of the early events of infection using a murine model have shown that the amoebae induce intense mucus secretion and an inflammatory reaction in the nasal cavity (Cervantes-Sandoval et al, 2008a;Rojas-Hernández et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri

et al. 2013

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Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis. This parasite invades its host by penetrating the olfactory mucosa. However, the mechanism of epithelium penetration is not well understood. In the present study, we evaluated the effect of N. fowleri trophozoites and the non-pathogenic Naegleria gruberi on Madin-Darby canine kidney (MDCK) tight junction proteins, including claudin-1, occludin and ZO-1, as well as on the actin cytoskeleton. Trophozoites from each of the free-living amoeba species were co-cultured with MDCK cells in a 1 : 1 ratio for 1, 3, 6 or 10 h. Light microscopy revealed that N. fowleri caused morphological changes as early as 3 h post-infection in an epithelial MDCK monolayer. Confocal microscopy analysis revealed that after 10 h of co-culture, N. fowleri trophozoites induced epithelial cell damage, which was characterized by changes in the actin apical ring and disruption of the ZO-1 and claudin-1 proteins but not occludin. Western blot assays revealed gradual degradation of ZO-1 and claudin-1 as early as 3 h post-infection. Likewise, there was a drop in transepithelial electrical resistance that resulted in increased epithelial permeability and facilitated the invasion of N. fowleri trophozoites by a paracellular route. In contrast, N. gruberi did not induce alterations in MDCK cells even at 10 h post-infection. Based on these results, we suggest that N. fowleri trophozoites disrupt epithelial monolayers, which could enable their penetration of the olfactory epithelium and subsequent invasion of the central nervous system.

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Description of a Naegleria sp. isolated from two cases of primary amoebic meningo‐encephalitis, and of the experimental pathological changes induced by it

Cited by 236 publications

References 32 publications

Impairment of O-antigen production confers resistance to grazing in a model amoeba–cyanobacterium predator–prey system

Impairment of O-antigen production confers resistance to grazing in a model amoeba–cyanobacterium predator–prey system

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri

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