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  1. Article ; Online: Studies on the cyst stage of Naegleria fowleri in vivo and in vitro.

    Evdokiou, Anna / Marciano-Cabral, Francine / Jamerson, Melissa

    The Journal of eukaryotic microbiology

    2022  Volume 69, Issue 2, Page(s) e12881

    Abstract: Naegleria fowleri is a pathogenic, free-living amoeba that causes primary amebic meningoencephalitis (PAM), a highly fatal disease of the central nervous system. N. fowleri demonstrates three forms: the trophozoite, flagellate, and cyst. Most studies ... ...

    Abstract Naegleria fowleri is a pathogenic, free-living amoeba that causes primary amebic meningoencephalitis (PAM), a highly fatal disease of the central nervous system. N. fowleri demonstrates three forms: the trophozoite, flagellate, and cyst. Most studies have focused on the trophozoite limiting information on the cyst. The present study examined the ability of cysts to attach to, excyst into the trophozoite form, and destroy cell cultures. Additionally, the study assessed the ability of cysts to cause PAM in a murine model. The results demonstrated that exposure to cysts and transformation into trophozoites resulted in destruction of cell cultures. Specifically, the mixed glial cells exhibited an increase in lactate dehydrogenase (LDH) release compared with cells without cyst exposure. On day eight postexposure, there was a nearly fourfold increase in LDH. The cysts of N. fowleri were shown not to be infective in vivo in a murine model. The mediation of the encystment process by the intracellular concentration of cAMP was also investigated. Trophozoites were treated with dipyridamole, an inhibitor of cAMP-specific phosphodiesterases. Dipyridamole increased the rate of encystment by nearly twofold and increased the intracellular concentration of cAMP in cysts by nearly sixfold throughout this period suggesting that cAMP is a mediator of encystment for N. fowleri.
    MeSH term(s) Amebiasis ; Animals ; Central Nervous System Protozoal Infections ; Cysts ; Dipyridamole ; Disease Models, Animal ; Mice ; Naegleria fowleri/physiology ; Trophozoites
    Chemical Substances Dipyridamole (64ALC7F90C)
    Language English
    Publishing date 2022-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12881
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  2. Article: Studies on the cyst stage of Naegleria fowleri in vivo and in vitro

    Evdokiou, Anna / Marciano‐Cabral, Francine / Jamerson, Melissa

    journal of eukaryotic microbiology. 2022 Mar., v. 69, no. 2

    2022  

    Abstract: Naegleria fowleri is a pathogenic, free‐living amoeba that causes primary amebic meningoencephalitis (PAM), a highly fatal disease of the central nervous system. N. fowleri demonstrates three forms: the trophozoite, flagellate, and cyst. Most studies ... ...

    Abstract Naegleria fowleri is a pathogenic, free‐living amoeba that causes primary amebic meningoencephalitis (PAM), a highly fatal disease of the central nervous system. N. fowleri demonstrates three forms: the trophozoite, flagellate, and cyst. Most studies have focused on the trophozoite limiting information on the cyst. The present study examined the ability of cysts to attach to, excyst into the trophozoite form, and destroy cell cultures. Additionally, the study assessed the ability of cysts to cause PAM in a murine model. The results demonstrated that exposure to cysts and transformation into trophozoites resulted in destruction of cell cultures. Specifically, the mixed glial cells exhibited an increase in lactate dehydrogenase (LDH) release compared with cells without cyst exposure. On day eight postexposure, there was a nearly fourfold increase in LDH. The cysts of N. fowleri were shown not to be infective in vivo in a murine model. The mediation of the encystment process by the intracellular concentration of cAMP was also investigated. Trophozoites were treated with dipyridamole, an inhibitor of cAMP‐specific phosphodiesterases. Dipyridamole increased the rate of encystment by nearly twofold and increased the intracellular concentration of cAMP in cysts by nearly sixfold throughout this period suggesting that cAMP is a mediator of encystment for N. fowleri.
    Keywords Naegleria fowleri ; animal models ; central nervous system ; dipyridamole ; encystment ; lactate dehydrogenase ; meningoencephalitis ; microbiology ; trophozoites
    Language English
    Dates of publication 2022-03
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12881
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  3. Article ; Online: The Effect of Different Environmental Conditions on the Viability of Naegleria fowleri Amoebae.

    Lam, Charlton / He, Li / Marciano-Cabral, Francine

    The Journal of eukaryotic microbiology

    2019  Volume 66, Issue 5, Page(s) 752–756

    Abstract: Naegleria fowleri, a free-living amoeba found in soil and freshwater environments, is the causative agent of Primary Amoebic Meningoencephalitis. Infection occurs when amoebae enter the nasal cavity, attach to the nasal mucosa and travel along olfactory ... ...

    Abstract Naegleria fowleri, a free-living amoeba found in soil and freshwater environments, is the causative agent of Primary Amoebic Meningoencephalitis. Infection occurs when amoebae enter the nasal cavity, attach to the nasal mucosa and travel along olfactory neurons towards the olfactory bulb. Upon reaching the central nervous system, the amoebae replicate very rapidly and can cause death in 3-10 days. Little is known about the conditions in which the amoeba can survive in the environment. We have tested conditions beyond the known boundaries on the viability of amoebae by introducing them into moderate and extreme salinity, pH, and temperatures. Our data shows that although viability expectedly decreases towards each of these extreme conditions, their tolerance was much greater than anticipated, including viability in moderate salinity, a wide pH range, and temperatures higher than the previously reported 45 °C.
    MeSH term(s) Amebiasis ; Animals ; Central Nervous System Protozoal Infections/parasitology ; Ecosystem ; Humans ; Hydrogen-Ion Concentration ; Naegleria fowleri/growth & development ; Naegleria fowleri/physiology ; Temperature
    Language English
    Publishing date 2019-04-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12719
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The Effect of Different Environmental Conditions on the Viability of Naegleria fowleri Amoebae

    Lam, Charlton / He, Li / Marciano‐Cabral, Francine

    journal of eukaryotic microbiology. 2019 Sept., v. 66, no. 5

    2019  

    Abstract: Naegleria fowleri, a free‐living amoeba found in soil and freshwater environments, is the causative agent of Primary Amoebic Meningoencephalitis. Infection occurs when amoebae enter the nasal cavity, attach to the nasal mucosa and travel along olfactory ... ...

    Abstract Naegleria fowleri, a free‐living amoeba found in soil and freshwater environments, is the causative agent of Primary Amoebic Meningoencephalitis. Infection occurs when amoebae enter the nasal cavity, attach to the nasal mucosa and travel along olfactory neurons towards the olfactory bulb. Upon reaching the central nervous system, the amoebae replicate very rapidly and can cause death in 3–10 days. Little is known about the conditions in which the amoeba can survive in the environment. We have tested conditions beyond the known boundaries on the viability of amoebae by introducing them into moderate and extreme salinity, pH, and temperatures. Our data shows that although viability expectedly decreases towards each of these extreme conditions, their tolerance was much greater than anticipated, including viability in moderate salinity, a wide pH range, and temperatures higher than the previously reported 45 °C.
    Keywords death ; environmental factors ; etiological agents ; freshwater ; meningoencephalitis ; Naegleria fowleri ; nasal cavity ; nasal mucosa ; neurons ; olfactory bulb ; pH ; salinity ; soil ; temperature ; viability
    Language English
    Dates of publication 2019-09
    Size p. 752-756.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12719
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  5. Article: Free-living amoebae as agents of human infection.

    Marciano-Cabral, Francine

    The Journal of infectious diseases

    2009  Volume 199, Issue 8, Page(s) 1104–1106

    MeSH term(s) Amebiasis/diagnosis ; Amebiasis/parasitology ; Amoebida/classification ; Amoebida/genetics ; Amoebida/pathogenicity ; Animals ; Humans ; Polymerase Chain Reaction/methods
    Language English
    Publishing date 2009-04-15
    Publishing country United States
    Document type Comment ; Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1086/597474
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  6. Article ; Online: Govinda s. Visvesvara: a tribute.

    Kaneshiro, Edna S / Marciano-Cabral, Francine / Moura, Hercules

    The Journal of eukaryotic microbiology

    2014  Volume 62, Issue 1, Page(s) 1–2

    MeSH term(s) Animals ; History, 20th Century ; History, 21st Century ; Humans ; India ; Microbiology/history ; Parasitology/history ; United States
    Language English
    Publishing date 2014-08-14
    Publishing country United States
    Document type Biography ; Festschrift ; Historical Article ; Portrait
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12143
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  7. Article ; Online: Identification of Naegleria fowleri proteins linked to primary amoebic meningoencephalitis.

    Jamerson, Melissa / Schmoyer, Jacqueline A / Park, Jay / Marciano-Cabral, Francine / Cabral, Guy A

    Microbiology (Reading, England)

    2017  Volume 163, Issue 3, Page(s) 322–332

    Abstract: Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis, a rapidly fatal disease of the central nervous system. N. fowleri can exist in cyst, flagellate or amoebic forms, depending on environmental conditions. The amoebic form can ... ...

    Abstract Naegleria fowleri (N. fowleri) causes primary amoebic meningoencephalitis, a rapidly fatal disease of the central nervous system. N. fowleri can exist in cyst, flagellate or amoebic forms, depending on environmental conditions. The amoebic form can invade the brain following introduction into the nasal passages. When applied intranasally to a mouse model, cultured N. fowleri amoebae exhibit low virulence. However, upon serial passage in mouse brain, the amoebae acquire a highly virulent state. In the present study, a proteomics approach was applied to the identification of N. fowleri amoeba proteins whose expression was associated with the highly virulent state in mice. Mice were inoculated intranasally with axenically cultured amoebae or with mouse-passaged amoebae. Examination by light and electron microscopy revealed no morphological differences. However, mouse-passaged amoebae were more virulent in mice as indicated by exhibiting a two log10 titre decrease in median infective dose 50 (ID50). Scatter plot analysis of amoebic lysates revealed a subset of proteins, the expression of which was associated with highly virulent amoebae. MS-MS indicated that this subset contained proteins that shared homology with those linked to cytoskeletal rearrangement and the invasion process. Invasion assays were performed in the presence of a select inhibitor to expand on the findings. The collective results suggest that N. fowleri gene products linked to cytoskeletal rearrangement and invasion may be candidate targets in the management of primary amoebic meningoencephalitis.
    MeSH term(s) Amebiasis/parasitology ; Amebiasis/pathology ; Animals ; Cell Adhesion/physiology ; Central Nervous System Protozoal Infections/parasitology ; Central Nervous System Protozoal Infections/pathology ; Disease Models, Animal ; Meningoencephalitis/parasitology ; Meningoencephalitis/pathology ; Mice ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Naegleria fowleri/pathogenicity ; Protozoan Proteins/metabolism ; Signal Transduction ; Virulence
    Chemical Substances Protozoan Proteins
    Language English
    Publishing date 2017-03-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.000428
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system.

    Lam, Charlton / Jamerson, Melissa / Cabral, Guy / Carlesso, Ana Maris / Marciano-Cabral, Francine

    Microbiology (Reading, England)

    2017  Volume 163, Issue 10, Page(s) 1436–1444

    Abstract: Naegleria fowleri is a free-living amoeba found in freshwater lakes and ponds and is the causative agent of primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system (CNS). PAM occurs when amoebae attach to the ... ...

    Abstract Naegleria fowleri is a free-living amoeba found in freshwater lakes and ponds and is the causative agent of primary amoebic meningoencephalitis (PAM), a rapidly fatal disease of the central nervous system (CNS). PAM occurs when amoebae attach to the nasal epithelium and invade the CNS, a process that involves binding to, and degradation of, extracellular matrix (ECM) components. This degradation is mediated by matrix metalloproteinases (MMPs), enzymes that have been described in other pathogenic protozoa, and that have been linked to their increased motility and invasive capability. These enzymes also are upregulated in tumorigenic cells and have been implicated in metastasis of certain tumours. In the present study, in vitro experiments linked MMPs functionally to the degradation of the ECM. Gelatin zymography demonstrated enzyme activity in N. fowleri whole cell lysates, conditioned media and media collected from invasion assays. Western immunoblotting indicated the presence of the metalloproteinases MMP-2 (gelatinase A), MMP-9 (gelatinase B) and MMP-14 [membrane type-1 matrix metalloproteinase (MT1-MMP)]. Highly virulent mouse-passaged amoebae expressed higher levels of MMPs than weakly virulent axenically grown amoebae. The functional relevance of MMPs in media was indicated through the use of the MMP inhibitor, 1,10-phenanthroline. The collective in vitro results suggest that MMPs play a critical role in vivo in invasion of the CNS and that these enzymes may be amenable targets for limiting PAM.
    MeSH term(s) Adolescent ; Animals ; Central Nervous System Protozoal Infections/parasitology ; Gene Expression ; Humans ; Matrix Metalloproteinase 14/genetics ; Matrix Metalloproteinase 14/metabolism ; Matrix Metalloproteinase 2/genetics ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/genetics ; Matrix Metalloproteinase 9/metabolism ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/metabolism ; Mice ; Naegleria fowleri/drug effects ; Naegleria fowleri/genetics ; Naegleria fowleri/pathogenicity ; Naegleria fowleri/ultrastructure ; Phenanthrolines/pharmacology ; Protease Inhibitors/pharmacology ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism
    Chemical Substances Phenanthrolines ; Protease Inhibitors ; Protozoan Proteins ; Matrix Metalloproteinases (EC 3.4.24.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Matrix Metalloproteinase 14 (EC 3.4.24.80) ; 1,10-phenanthroline (W4X6ZO7939)
    Language English
    Publishing date 2017-09-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.000537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Advances in free-living amebae research 2006: summary from the IX International Workshop on Opportunistic Protists (IWOP-9).

    Marciano-Cabral, Francine

    The Journal of eukaryotic microbiology

    2006  Volume 53 Suppl 1, Page(s) S8–9

    MeSH term(s) Amebiasis/complications ; Amebiasis/immunology ; Amebiasis/parasitology ; Amoeba/classification ; Amoeba/immunology ; Amoeba/isolation & purification ; Animals ; Encephalitis/microbiology ; Environmental Microbiology ; Humans ; Keratitis/microbiology ; Meningoencephalitis/parasitology
    Language English
    Publishing date 2006
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/j.1550-7408.2006.00155.x
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  10. Article ; Online: Identification of peptidases in highly pathogenic vs. weakly pathogenic Naegleria fowleri amebae.

    Vyas, Ishan K / Jamerson, Melissa / Cabral, Guy A / Marciano-Cabral, Francine

    The Journal of eukaryotic microbiology

    2014  Volume 62, Issue 1, Page(s) 51–59

    Abstract: Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic Meningoencephalitis. Highly pathogenic mouse-passaged amebae (Mp) and weakly pathogenic axenically grown (Ax) N. fowleri were examined for peptidase activity. Zymography and ...

    Abstract Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic Meningoencephalitis. Highly pathogenic mouse-passaged amebae (Mp) and weakly pathogenic axenically grown (Ax) N. fowleri were examined for peptidase activity. Zymography and azocasein peptidase activity assays demonstrated that Mp and Ax N. fowleri exhibited a similar peptidase pattern. Prominent for whole cell lysates, membranes and conditioned medium (CM) from Mp and Ax amebae was the presence of an activity band of approximately 58 kDa that was sensitive to E64, a cysteine peptidase inhibitor. However, axenically grown N. fowleri demonstrated a high level of this peptidase activity in membrane preparations. The inhibitor E64 also reduced peptidase activity in ameba-CM consistent with the presence of secreted cysteine peptidases. Exposure of Mp amebae to E64 reduced their migration through matrigel that was used as an extracellular matrix, suggesting a role for cysteine peptidases in invasion of the central nervous system (CNS). The collective results suggest that the profile of peptidases is not a discriminative marker for distinguishing Mp from Ax N. fowleri. However, the presence of a prominent level of activity for cysteine peptidases in N. fowleri membranes and CM, suggests that these enzymes may serve to facilitate passage of the amebae into the CNS.
    MeSH term(s) Adolescent ; Amebiasis/cerebrospinal fluid ; Amebiasis/parasitology ; Animals ; Axenic Culture ; Cell Fractionation ; Cell Membrane/chemistry ; Cell Membrane/drug effects ; Cell Membrane/enzymology ; Cell Movement/drug effects ; Central Nervous System Protozoal Infections/cerebrospinal fluid ; Central Nervous System Protozoal Infections/parasitology ; Collagen ; Culture Media, Conditioned/chemistry ; Culture Media, Conditioned/metabolism ; Cysteine Proteases/chemistry ; Cysteine Proteases/isolation & purification ; Cysteine Proteinase Inhibitors/pharmacology ; Drug Combinations ; Female ; Humans ; Laminin ; Leucine/analogs & derivatives ; Leucine/pharmacology ; Mice ; Naegleria fowleri/drug effects ; Naegleria fowleri/enzymology ; Naegleria fowleri/isolation & purification ; Naegleria fowleri/pathogenicity ; Proteoglycans ; Protozoan Proteins/antagonists & inhibitors ; Protozoan Proteins/chemistry ; Protozoan Proteins/isolation & purification
    Chemical Substances Culture Media, Conditioned ; Cysteine Proteinase Inhibitors ; Drug Combinations ; Laminin ; Proteoglycans ; Protozoan Proteins ; matrigel (119978-18-6) ; Collagen (9007-34-5) ; Cysteine Proteases (EC 3.4.-) ; Leucine (GMW67QNF9C) ; E 64 (R76F7856MV)
    Language English
    Publishing date 2014-08-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1147218-2
    ISSN 1550-7408 ; 1066-5234
    ISSN (online) 1550-7408
    ISSN 1066-5234
    DOI 10.1111/jeu.12152
    Database MEDical Literature Analysis and Retrieval System OnLINE

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