Azithromycin disrupts apicoplast biogenesis in replicating and dormant liver stages of the relapsing malaria parasites Plasmodium vivax and Plasmodium cynomolgi.

Autor: Amanzougaghene N; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France., Tajeri S; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Franetich JF; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Ashraf K; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Soulard V; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Bigeard P; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Guindo CO; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France., Bouillier C; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France., Lemaitre J; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France., Relouzat F; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France., Legrand R; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France., Kocken CHM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Zeeman AM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Roobsoong W; Mahidol Vivax Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok, Thailand., Sattabongkot J; Mahidol Vivax Research Unit, Faculty of Tropical Medicine Mahidol University, Bangkok, Thailand., Yang Z; Department of Pathogen Biology and Immunology, Kunming Medical University, Chenggong New Town, Kunming, Yunnan Province,China., Snounou G; Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), Fontenay-aux-Roses and Kremlin-Bicêtre, France. Electronic address: gsnounou@gmail.com., Mazier D; Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France. Electronic address: dominique.mazier@sorbonne-universite.fr.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 May; Vol. 63 (5), pp. 107112. Date of Electronic Publication: 2024 Feb 15.
DOI: 10.1016/j.ijantimicag.2024.107112
Abstrakt: The control and elimination of malaria caused by Plasmodium vivax is hampered by the threat of relapsed infection resulting from the activation of dormant hepatic hypnozoites. Currently, only the 8-aminoquinolines, primaquine and tafenoquine, have been approved for the elimination of hypnozoites, although their use is hampered by potential toxicity. Therefore, an alternative radical curative drug that safely eliminates hypnozoites is a pressing need. This study assessed the potential hypnozoiticidal activity of the antibiotic azithromycin, which is thought to exert antimalarial activity by inhibiting prokaryote-like ribosomal translation within the apicoplast, an indispensable organelle. The results show that azithromycin inhibited apicoplast development during liver-stage schizogony in P. vivax and Plasmodium cynomolgi, leading to impaired parasite maturation. More importantly, this study found that azithromycin is likely to impair the hypnozoite's apicoplast, resulting in the loss of this organelle. Subsequently, using a recently developed long-term hepatocyte culture system, this study found that this loss likely induces a delay in the hypnozoite activation rate, and that those parasites that do proceed to schizogony display liver-stage arrest prior to differentiating into hepatic merozoites, thus potentially preventing relapse. Overall, this work provides evidence for the potential use of azithromycin for the radical cure of relapsing malaria, and identifies apicoplast functions as potential drug targets in quiescent hypnozoites.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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