scholarly journals In Vitro Effects of Amphotericin B on Growth and Ultrastructure of the Amoeboflagellates Naegleria gruberi and Naegleria fowleri

1975 ◽  
Vol 8 (5) ◽  
pp. 591-605 ◽  
Author(s):  
F. L. Schuster ◽  
E. Rechthand
Keyword(s):  
Amphotericin B ◽  
Naegleria Fowleri ◽  
In Vitro Effects ◽  
Nægleria Fowleri ◽  
Naegleria Gruberi

scholarly journals Synergistic Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

2006 ◽  
Vol 51 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Shannon M. Soltow ◽  
George M. Brenner
Keyword(s):  
Central Nervous System ◽  
Mouse Model ◽  
Amphotericin B ◽  
Fixed Combination ◽  
Central Nervous System Infection ◽  
Naegleria Fowleri ◽  
Combined Use ◽  
Nægleria Fowleri ◽  
Primary Amebic Meningoencephalitis

ABSTRACT Naegleria fowleri is responsible for producing a rapidly fatal central nervous system infection known as primary amebic meningoencephalitis (PAM). To date, amphotericin B, an antifungal agent, is the only agent with established clinical efficacy in the treatment of PAM. However, amphotericin B is not always successful in treating PAM and is associated with severe adverse effects. We previously found azithromycin to be more effective than amphotericin B in a mouse model of PAM. We therefore investigated the combination of amphotericin B and azithromycin in vitro and in a mouse model of PAM. For the in vitro studies, 50% inhibitory concentrations were calculated for each drug alone and for the drugs in fixed combination ratios of 1:1, 3:1, and 1:3. We found amphotericin B and azithromycin to be synergistic at all three of the fixed combination ratios. In our mouse model of PAM, a combination of amphotericin B (2.5 mg/kg of body weight) and azithromycin (25 mg/kg) protected 100% of the mice, whereas amphotericin B alone (2.5 mg/kg) protected only 27% of mice and azithromycin alone (25 mg/kg) protected 40% of mice. This study indicates that amphotericin B and azithromycin are synergistic against the Lee strain of N. fowleri, suggesting that the combined use of these agents may be beneficial in treating PAM.

Oleic Acid Coated Silver Nanoparticles Showed Better in Vitro Amoebicidal Effects against Naegleria fowleri than Amphotericin B

2019 ◽  
Vol 11 (16) ◽  
pp. 2431-2437 ◽  
Author(s):  
Kavitha Rajendran ◽  
Ayaz Anwar ◽  
Naveed Ahmed Khan ◽  
Zara Aslam ◽  
Muhammad Raza Shah ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Oleic Acid ◽  
Amphotericin B ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri

scholarly journals Amphotericin B induces apoptosis-like programmed cell death in Naegleria fowleri and Naegleria gruberi

Microbiology ◽  
2017 ◽  
Vol 163 (7) ◽  
pp. 940-949 ◽  
Author(s):  
Roberto Cárdenas-Zúñiga ◽  
Angélica Silva-Olivares ◽  
José D' Artagnan Villalba-Magdaleno ◽  
Virginia Sánchez-Monroy ◽  
Jesús Serrano-Luna ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Amphotericin B ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri ◽  
Naegleria Gruberi

scholarly journals Expression of the nfa1 Gene Cloned from Pathogenic Naegleria fowleri in Nonpathogenic N. gruberi Enhances Cytotoxicity against CHO Target Cells In Vitro

2005 ◽  
Vol 73 (7) ◽  
pp. 4098-4105 ◽  
Author(s):  
Seok-Ryoul Jeong ◽  
Sang-Chul Lee ◽  
Kyoung-Ju Song ◽  
Sun Park ◽  
Kyongmin Kim ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Target Cells ◽  
Naegleria Fowleri ◽  
Specific Primers ◽  
Reading Frame ◽  
Reverse Transcription Pcr ◽  
Nægleria Fowleri ◽  
Green Fluorescent ◽  
Naegleria Gruberi

ABSTRACT The pathogenic amoeba Naegleria fowleri has a 360-bp nfa1 gene that encodes the Nfa1 protein (13.1 kDa), which is located in the pseudopodia of the amoeba, and an anti-Nfa1 antibody reduces N. fowleri-induced mammalian-cell cytotoxicity in vitro. In contrast, an anti-Nfa1 antibody cannot detect Nfa1 protein expression in the nonpathogenic amoeba Naegleria gruberi, which also possesses the nfa1 gene. In the present study, the nfa1 gene cloned from pathogenic N. fowleri was transfected into nonpathogenic N. gruberi to determine whether it was related to pathogenicity. The nfa1 gene was initially inserted into a eukaryotic transfection vector, pEGFP-C2, containing a cytomegalovirus promoter and the green fluorescent protein (GFP) gene, and was designed as pEGFP-C2/nfa1UTR (nfa1UTR contains 5′ upstream regions, the nfa1 open reading frame, and 3′ downstream regions). After transfection, the green fluorescence was observed in the cytoplasm of N. gruberi trophozoites. These transfectants were preserved for more than 9 months after selection. The transfected nfa1 gene was observed by PCR using nfa1- and vector-specific primers in the genomic DNA of N. gruberi transfected with the pEGFP-C2/nfa1UTR vector. In addition, the nfa1 and GFP genes were identified by reverse transcription-PCR in transgenic N. gruberi. The Nfa1 protein expressed in transgenic N. gruberi was identified as a 13.1-kDa band by Western blotting using an anti-Nfa1 antibody. Finally, N. gruberi transfected with the pEGFP-C2/nfa1UTR vector was found to have enhanced cytotoxicity against CHO cells compared with naïve N. gruberi.

scholarly journals Activities of Azithromycin and Amphotericin B against Naegleria fowleri In Vitro and in a Mouse Model of Primary Amebic Meningoencephalitis

2003 ◽  
Vol 47 (2) ◽  
pp. 524-528 ◽  
Author(s):  
Shannon M. Goswick ◽  
George M. Brenner
Keyword(s):  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri ◽  
Free Living Ameba ◽  
Primary Amebic Meningoencephalitis ◽  
Observation Period

ABSTRACT Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 μM (10 μg/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 μM (0.1 μg/ml). Azithromycin protected 100% of mice infected with N. fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.

scholarly journals In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 689
Author(s):  
Hye Jee Hahn ◽  
Anjan Debnath
Keyword(s):  
Amphotericin B ◽  
Mevalonate Pathway ◽  
Unmet Need ◽  
Drug Regimen ◽  
Naegleria Fowleri ◽  
Protein Farnesyltransferase ◽  
Nægleria Fowleri ◽  
Different Strains ◽  
Coa Reductase

Free-living amoeba Naegleria fowleri causes a rapidly fatal infection primary amebic meningoencephalitis (PAM) in children. The drug of choice in treating PAM is amphotericin B, but very few patients treated with amphotericin B have survived PAM. Therefore, development of efficient drugs is a critical unmet need. We identified that the FDA-approved pitavastatin, an inhibitor of HMG Co-A reductase involved in the mevalonate pathway, was equipotent to amphotericin B against N. fowleri trophozoites. The genome of N. fowleri contains a gene encoding protein farnesyltransferase (FT), the last common enzyme for products derived from the mevalonate pathway. Here, we show that a clinically advanced FT inhibitor lonafarnib is active against different strains of N. fowleri with EC50 ranging from 1.5 to 9.2 µM. A combination of lonafarnib and pitavastatin at different ratios led to 95% growth inhibition of trophozoites and the combination achieved a dose reduction of about 2- to 28-fold for lonafarnib and 5- to 30-fold for pitavastatin. No trophozoite with normal morphology was found when trophozoites were treated for 48 h with a combination of 1.7 µM each of lonafarnib and pitavastatin. Combination of lonafarnib and pitavastatin may contribute to the development of a new drug regimen for the treatment of PAM.

scholarly journals Effect of Therapeutic Chemical Agents In Vitro and on Experimental Meningoencephalitis Due to Naegleria fowleri

2008 ◽  
Vol 52 (11) ◽  
pp. 4010-4016 ◽  
Author(s):  
Jong-Hyun Kim ◽  
Suk-Yul Jung ◽  
Yang-Jin Lee ◽  
Kyoung-Ju Song ◽  
Daeho Kwon ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Survival Rates ◽  
Laboratory Animals ◽  
Naegleria Fowleri ◽  
Time To Death ◽  
Nægleria Fowleri ◽  
Amoebic Meningoencephalitis ◽  
Mean Time

ABSTRACT Naegleria fowleri is a ubiquitous, pathogenic free-living amoeba; it is the most virulent Naegleria species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for N. fowleri infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic N. fowleri. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When N. fowleri trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 μg/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by N. fowleri, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.

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