Parasites, Hosts and Diseases

"Naegleria fowleri"

Case Report

A Fatal Case of Naegleria fowleri Meningoencephalitis in Taiwan: Mei-Yu Su, Ming-Shih Lee, Ling-Yuh Shyu, Wei-Chen Lin, Pei-Ching Hsiao, Chi-Ping Wang, Dar-Der Ji, Ke-Min Chen, Shih-Chan Lai; Korean J Parasitol 2013;51(2):203-206.
Published online April 25, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.2.203

Abstract
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After bathing at a hot spring resort, a 75-year-old man presented to the emergency department because of seizure-like attack with loss of conscious. This is the first case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in Taiwan. PAM was diagnosed based on detection of actively motile trophozoites in cerebrospinal fluid using a wet-mount smear and the Liu's stain. The amoebae were further confirmed by PCR and gene sequencing. In spite of administering amphotericin B treatment, the patient died 25 days later.

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European Journal of Protistology.2015; 51(5): 401. CrossRef

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Brief Communication

Naegleria fowleri Lysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells: Yang-Jin Lee, Chang-Eun Park, Jong-Hyun Kim, Hae-Jin Sohn, Jinyoung Lee, Suk-Yul Jung, Ho-Joon Shin; Korean J Parasitol 2011;49(3):285-290.
Published online September 30, 2011; DOI: https://doi.org/10.3347/kjp.2011.49.3.285

Abstract
PDF

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A ⁵¹Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.

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Transcriptomic profiling of “brain-eating amoeba” Naegleria fowleri infection in mice: the host and the protozoa perspectives
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Hương Giang Lê, Jung-Mi Kang, Tuấn Cường Võ, Won Gi Yoo, Byoung-Kuk Na
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Naegleria fowleri Cathepsin B Induces a Pro-Inflammatory Immune Response in BV-2 Microglial Cells via NF-κB and AP-1 Dependent-MAPK Signaling Pathway
Hương Giang Lê, Jung-Mi Kang, Tuấn Cường Võ, Byoung-Kuk Na
International Journal of Molecular Sciences.2022; 23(15): 8388. CrossRef
Parasite infections, neuroinflammation, and potential contributions of gut microbiota
Jérémy Alloo, Ines Leleu, Corinne Grangette, Sylviane Pied
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Fowlerstefin, a cysteine protease inhibitor of Naegleria fowleri, induces inflammatory responses in BV-2 microglial cells in vitro
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Original Articles

Contact-Independent Cell Death of Human Microglial Cells due to Pathogenic Naegleria fowleri Trophozoites: Jong-Hyun Kim, Daesik Kim, Ho-Joon Shin; Korean J Parasitol 2008;46(4):217-221.
Published online December 20, 2008; DOI: https://doi.org/10.3347/kjp.2008.46.4.217

Abstract
PDF

Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increasse of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

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Scientific Reports.2025;[Epub] CrossRef
Advances in the study of extracellular vesicles of Naegleria fowleri and their role in contact-independent pathogenic mechanisms
Ismael Castelan-Ramírez, Catalina Flores-Maldonado, Dolores Hernández-Martínez, Lizbeth Salazar-Villatoro, Alberto Daniel Saucedo-Campos, David Segura-Cobos, Adolfo René Méndez-Cruz, Maritza Omaña-Molina
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Extracellular Vesicles from Naegleria fowleri Induce IL-8 Response in THP-1 Macrophage
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Fowlerstefin, a cysteine protease inhibitor of Naegleria fowleri, induces inflammatory responses in BV-2 microglial cells in vitro
Thị Lam Thái, Jung-Mi Kang, Hương Giang Lê, Jinyoung Lee, Won Gi Yoo, Ho-Joon Shin, Woon-Mok Sohn, Byoung-Kuk Na
Parasites & Vectors.2020;[Epub] CrossRef
Cellular characterization of actin gene concerned with contact‐dependent mechanisms in Naegleria fowleri
Hae‐Jin Sohn, Kyoung‐Ju Song, Heekyoung Kang, A‐Jeong Ham, Jae‐Ho Lee, Yong‐Joon Chwae, Kyongmin Kim, Sun Park, Jong‐Hyun Kim, Ho‐Joon Shin
Parasite Immunology.2019;[Epub] CrossRef
Cytopathic Change and Inflammatory Response of Human Corneal Epithelial Cells Induced by Acanthamoeba castellanii Trophozoites and Cysts
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Experimental Parasitology.2017; 183: 171. CrossRef
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Ruqaiyyah Siddiqui, Ibne Karim M. Ali, Jennifer R. Cope, Naveed Ahmed Khan
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NLRP3 Inflammasome Activation in THP-1 Target Cells Triggered by Pathogenic Naegleria fowleri
Jong-Hyun Kim, Hae-Jin Sohn, Jong-Kyun Yoo, Heekyoung Kang, Gi-Sang Seong, Yong-Joon Chwae, Kyongmin Kim, Sun Park, Ho-Joon Shin, J. A. Appleton
Infection and Immunity.2016; 84(9): 2422. CrossRef
Novel cathepsin B and cathepsin B-like cysteine protease of Naegleria fowleri excretory–secretory proteins and their biochemical properties
Jinyoung Lee, Jong-Hyun Kim, Hae-Jin Sohn, Hee-Jong Yang, Byoung-Kuk Na, Yong-Joon Chwae, Sun Park, Kyongmin Kim, Ho-Joon Shin
Parasitology Research.2014; 113(8): 2765. CrossRef
Naegleria fowleriLysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells
Yang-Jin Lee, Chang-Eun Park, Jong-Hyun Kim, Hae-Jin Sohn, Jinyoung Lee, Suk-Yul Jung, Ho-Joon Shin
The Korean Journal of Parasitology.2011; 49(3): 285. CrossRef
Screening of Swiss hot spring resorts for potentially pathogenic free-living amoebae
Christian Gianinazzi, Marc Schild, Beatrice Zumkehr, Fritz Wüthrich, Irina Nüesch, Regula Ryter, Nadia Schürch, Bruno Gottstein, Norbert Müller
Experimental Parasitology.2010; 126(1): 45. CrossRef
Immunodominant antigens in Naegleria fowleri excretory–secretory proteins were potential pathogenic factors
Jong-Hyun Kim, Ae-Hee Yang, Hae-Jin Sohn, Daesik Kim, Kyoung-Ju Song, Ho-Joon Shin
Parasitology Research.2009; 105(6): 1675. CrossRef

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Decreasing effect of an anti-Nfa1 polyclonal antibody on the in vitro cytotoxicity of pathogenic Naegleria fowleri: Seok-Ryoul Jeong, Su-Yeon Kang, Sang-Chul Lee, Kyoung-Ju Song, Kyung-il Im, Ho-Joon Shin; Korean J Parasitol 2004;42(1):35-40.
Published online March 20, 2004; DOI: https://doi.org/10.3347/kjp.2004.42.1.35

Abstract
PDF

The nfa1 gene was cloned from a cDNA library of pathogenic Naegleria fowleri by immunoscreening; it consisted of 360 bp and produced a 13.1 kDa recombinant protein (rNfa1) that showed the pseudopodia-specific localization by immunocytochemistry in the previous study. Based on the idea that the pseudopodia-specific Nfa1 protein mentioned above seems to be involved in the pathogenicity of N. fowleri, we observed the effect of an anti-Nfa1 antibody on the proliferation of N. fowleri trophozoites and the cytotoxicity of N. fowleri trophozoites on the target cells. The proliferation of N. fowleri trophozoites was inhibited after being treated with an anti-Nfa1 polyclonal antibody in a dose-dependent manner for 48 hrs. By a light microscope, CHO cells co-cultured with N. fowleri trophozoites (group I) for 48 hrs showed severe morphological destruction. On the contrary, CHO cells co-cultured with N. fowleri trophozoites and anti-Nfa1 polyclonal antibody (1:100 dilution) (group II) showed less destruction. In the LDH release assay results, group I showed 50.6% cytotoxicity, and group II showed 39.3%. Consequently, addition of an anti-Nfa1 polyclonal antibody produced a decreasing effect of in vitro cytotoxicity of N. fowleri in a dosedependent manner.

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Naegleria fowleriLysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells
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Parasitology Research.2009; 105(6): 1675. CrossRef
Contact-Independent Cell Death of Human Microglial Cells due to Pathogenic Naegleria fowleri Trophozoites
Jong-Hyun Kim, Daesik Kim, Ho-Joon Shin
The Korean Journal of Parasitology.2008; 46(4): 217. CrossRef
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