In vitro activity of eravacycline, a novel synthetic halogenated tetracycline, against the malaria parasite Plasmodium falciparum. (March 2021)

• Record Type: Journal Article
• Authors: Koehne, Erik; Kreidenweiss, Andrea; Adegbite, Bayode Romeo; Manego, Rella Zoleko; McCall, Matthew B.B.; Mombo-Ngoma, Ghyslain; Adegnika, Ayola Akim; Agnandji, Sélidji Todagbé; Mordmüller, Benjamin; Held, Jana
• Is Part Of: Journal of global antimicrobial resistance. Volume 24(2021)
• Page Start: 93
• Page End: 97
• Publication Date: 2021-03
• Subjects: Plasmodium falciparum -- Eravacycline -- Tetracycline -- Isopentenyl pyrophosphate -- Malaria; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2020.11.024
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Eravacycline has superior in vitro activity against P. falciparum . This is in comparison with other tetracyclines. This has potential as a novel antibiotic. The apicoplast is indicated as the target organelle of eravacycline. Malaria combination containing antibiotic could be used for bacterial co-infection. Abstract: 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.