In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum
Objectives: Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites...
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Format: | Article |
Language: | English |
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Elsevier
2021-03-01
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Series: | Journal of Global Antimicrobial Resistance |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716520303106 |
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doaj-5f396db5dc224c23a90809c125387fba |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erik Koehne Andrea Kreidenweiss Bayode Romeo Adegbite Rella Zoleko Manego Matthew B.B. McCall Ghyslain Mombo-Ngoma Ayola Akim Adegnika Sélidji Todagbé Agnandji Benjamin Mordmüller Jana Held |
spellingShingle |
Erik Koehne Andrea Kreidenweiss Bayode Romeo Adegbite Rella Zoleko Manego Matthew B.B. McCall Ghyslain Mombo-Ngoma Ayola Akim Adegnika Sélidji Todagbé Agnandji Benjamin Mordmüller Jana Held In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum Journal of Global Antimicrobial Resistance Plasmodium falciparum Eravacycline Tetracycline Isopentenyl pyrophosphate Malaria |
author_facet |
Erik Koehne Andrea Kreidenweiss Bayode Romeo Adegbite Rella Zoleko Manego Matthew B.B. McCall Ghyslain Mombo-Ngoma Ayola Akim Adegnika Sélidji Todagbé Agnandji Benjamin Mordmüller Jana Held |
author_sort |
Erik Koehne |
title |
In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum |
title_short |
In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum |
title_full |
In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum |
title_fullStr |
In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum |
title_full_unstemmed |
In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum |
title_sort |
in vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite plasmodium falciparum |
publisher |
Elsevier |
series |
Journal of Global Antimicrobial Resistance |
issn |
2213-7165 |
publishDate |
2021-03-01 |
description |
Objectives: Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites renders the search for new treatment candidates urgent. We determined the in vitro potency of eravacycline against Plasmodium falciparum and investigated the apicoplast as a potential drug target. Methods: Four tetracyclines, including eravacycline, tetracycline, tigecycline, and doxycycline, and the lincosamide clindamycin, were tested in 3-day and 6-day in vitro susceptibility assays of P. falciparum laboratory strain 3D7 and/or of clinical isolates obtained from 33 P. falciparum infected individuals from Gabon in 2018. Assays with isopentenyl pyrophosphate substitution were performed to investigate whether apicoplast-encoded isoprenoid biosynthesis is inhibited by these antibiotics. Results: Eravacycline showed the highest activity of all tetracyclines tested in clinical isolates in the 3-day and 6-day assays. Substitution of isopentenyl pyrophosphate in vitro using the laboratory strain 3D7 reversed the activity of eravacycline and comparator antibiotics, indicating the apicoplast to be the main target organelle. Conclusions: These results demonstrate the potential of novel antibiotics, and eravacycline, as candidate antimalarial therapies. |
topic |
Plasmodium falciparum Eravacycline Tetracycline Isopentenyl pyrophosphate Malaria |
url |
http://www.sciencedirect.com/science/article/pii/S2213716520303106 |
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doaj-5f396db5dc224c23a90809c125387fba2021-06-09T05:58:08ZengElsevierJournal of Global Antimicrobial Resistance2213-71652021-03-01249397In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparumErik Koehne0Andrea Kreidenweiss1Bayode Romeo Adegbite2Rella Zoleko Manego3Matthew B.B. McCall4Ghyslain Mombo-Ngoma5Ayola Akim Adegnika6Sélidji Todagbé Agnandji7Benjamin Mordmüller8Jana Held9Institute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyCentre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, GabonCentre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep of Medicine, University Medical Center Hamburg-Eppendorf, Bernhard-Nocht-Straße 74, D-20359 Hamburg, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Dep of Medicine, University Medical Center Hamburg-Eppendorf, Bernhard-Nocht-Straße 74, D-20359 Hamburg, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, GermanyInstitute of Tropical Medicine, Eberhard Karls University Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, B.P. 242, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany; Corresponding author at: Institute of Tropical Medicine, Eberhard-Karls University, Wilhelmstraße 27, D-72074 Tübingen, Germany.Objectives: Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites renders the search for new treatment candidates urgent. We determined the in vitro potency of eravacycline against Plasmodium falciparum and investigated the apicoplast as a potential drug target. Methods: Four tetracyclines, including eravacycline, tetracycline, tigecycline, and doxycycline, and the lincosamide clindamycin, were tested in 3-day and 6-day in vitro susceptibility assays of P. falciparum laboratory strain 3D7 and/or of clinical isolates obtained from 33 P. falciparum infected individuals from Gabon in 2018. Assays with isopentenyl pyrophosphate substitution were performed to investigate whether apicoplast-encoded isoprenoid biosynthesis is inhibited by these antibiotics. Results: Eravacycline showed the highest activity of all tetracyclines tested in clinical isolates in the 3-day and 6-day assays. Substitution of isopentenyl pyrophosphate in vitro using the laboratory strain 3D7 reversed the activity of eravacycline and comparator antibiotics, indicating the apicoplast to be the main target organelle. Conclusions: These results demonstrate the potential of novel antibiotics, and eravacycline, as candidate antimalarial therapies.http://www.sciencedirect.com/science/article/pii/S2213716520303106Plasmodium falciparumEravacyclineTetracyclineIsopentenyl pyrophosphateMalaria |