Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri
Naegleria fowleri is both a pathogenic and a free-living microbial eukaryote, responsible for the development of primary amoebic meningoencephalitis (PAM) in humans. PAM is a rapid, severe and fatal underestimated infectious disease, which has been reported in countries with warmer climates. The maj...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221132072100052X |
| _version_ | 1819099981768818688 |
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| author | Rubén Martín-Escolano Lyto Yiangou Eleanna Kazana Gary K. Robinson Martin Michaelis Anastasios D. Tsaousis |
| author_facet | Rubén Martín-Escolano Lyto Yiangou Eleanna Kazana Gary K. Robinson Martin Michaelis Anastasios D. Tsaousis |
| author_sort | Rubén Martín-Escolano |
| collection | DOAJ |
| description | Naegleria fowleri is both a pathogenic and a free-living microbial eukaryote, responsible for the development of primary amoebic meningoencephalitis (PAM) in humans. PAM is a rapid, severe and fatal underestimated infectious disease, which has been reported in countries with warmer climates. The major drawbacks with PAM are the lack of effective therapies and delay in diagnosis. The current frontline treatment presents a low rate of recovery (5%) and severe adverse effects. For example, many drug candidates lack efficacy, since they do not effectively cross the blood-brain-barrier. Consequently, more effective drugs are urgently needed. Herein, we report a new in vitro method suitable for medium- and high-throughput drug discovery assays, using the closely related Naegleria gruberi as a model. We have subsequently used this method to screen a library of 1175 Food and Drug Administration-approved drugs. As a result, we present three drugs (camptothecin, pyrimethamine, and terbinafine) that can be repurposed, and are anticipated to readily cross the blood-brain-barrier with activity against Naegleria species in therapeutically achievable concentrations. Successively, we integrated several in vitro assays that resulted in identifying fast-acting and high amoebicidal drugs. In conclusion, we present a new approach for the identification of anti-Naegleria drugs along with three potential drug candidates for further development for the treatment of PAM. |
| first_indexed | 2024-12-22T00:55:31Z |
| format | Article |
| id | doaj.art-7e8082d5333045b99e7ac7c59f598123 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-22T00:55:31Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-7e8082d5333045b99e7ac7c59f5981232022-12-21T18:44:19ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-12-0117204212Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleriRubén Martín-Escolano0Lyto Yiangou1Eleanna Kazana2Gary K. Robinson3Martin Michaelis4Anastasios D. Tsaousis5Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UKLaboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK; School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UKLaboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UKSchool of Biosciences, University of Kent, Canterbury, CT2 7NJ, UKSchool of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK; Corresponding author.Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK; School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK; Corresponding author. Laboratory of Molecular & Evolutionary Parasitology, RAPID Group, School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.Naegleria fowleri is both a pathogenic and a free-living microbial eukaryote, responsible for the development of primary amoebic meningoencephalitis (PAM) in humans. PAM is a rapid, severe and fatal underestimated infectious disease, which has been reported in countries with warmer climates. The major drawbacks with PAM are the lack of effective therapies and delay in diagnosis. The current frontline treatment presents a low rate of recovery (5%) and severe adverse effects. For example, many drug candidates lack efficacy, since they do not effectively cross the blood-brain-barrier. Consequently, more effective drugs are urgently needed. Herein, we report a new in vitro method suitable for medium- and high-throughput drug discovery assays, using the closely related Naegleria gruberi as a model. We have subsequently used this method to screen a library of 1175 Food and Drug Administration-approved drugs. As a result, we present three drugs (camptothecin, pyrimethamine, and terbinafine) that can be repurposed, and are anticipated to readily cross the blood-brain-barrier with activity against Naegleria species in therapeutically achievable concentrations. Successively, we integrated several in vitro assays that resulted in identifying fast-acting and high amoebicidal drugs. In conclusion, we present a new approach for the identification of anti-Naegleria drugs along with three potential drug candidates for further development for the treatment of PAM.http://www.sciencedirect.com/science/article/pii/S221132072100052XNaegleriaBrain-eating amoebaPAMDrug screeningDrug repurposing |
| spellingShingle | Rubén Martín-Escolano Lyto Yiangou Eleanna Kazana Gary K. Robinson Martin Michaelis Anastasios D. Tsaousis Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri International Journal for Parasitology: Drugs and Drug Resistance Naegleria Brain-eating amoeba PAM Drug screening Drug repurposing |
| title | Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri |
| title_full | Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri |
| title_fullStr | Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri |
| title_full_unstemmed | Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri |
| title_short | Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri |
| title_sort | repurposing in vitro approaches for screening anti parasitic drugs against the brain eating amoeba naegleria fowleri |
| topic | Naegleria Brain-eating amoeba PAM Drug screening Drug repurposing |
| url | http://www.sciencedirect.com/science/article/pii/S221132072100052X |
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