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Antimicrob Agents Chemother. 2017 May 24;61(6). pii: e02699-16. doi: 10.1128/AAC.02699-16. Print 2017 Jun.

Bioluminescence Method for In Vitro Screening of Plasmodium Transmission-Blocking Compounds.

Author information

1
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
2
Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
3
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal antoniomendes@medicina.ulisboa.pt mprudencio@medicina.ulisboa.pt.

Abstract

The sporogonic stage of the life cycle of Plasmodium spp., the causative agents of malaria, occurs inside the parasite's mosquito vector, where a process of fertilization, meiosis, and mitotic divisions culminates in the generation of large numbers of mammalian-infective sporozoites. Efforts to cultivate Plasmodium mosquito stages in vitro have proved challenging and yielded only moderate success. Here, we describe a methodology that simplifies the in vitro screening of much-needed transmission-blocking (TB) compounds employing a bioluminescence-based method to monitor the in vitro development of sporogonic stages of the rodent malaria parasite Plasmodium berghei Our proof-of-principle assessment of the in vitro TB activity of several commonly used antimalarial compounds identified cycloheximide, thiostrepton, and atovaquone as the most active compounds against the parasite's sporogonic stages. The TB activity of these compounds was further confirmed by in vivo studies that validated our newly developed in vitro approach to TB compound screening.

KEYWORDS:

Plasmodium berghei; in vitro cultures; malaria; mosquito stages; sporogony

PMID:
28348156
PMCID:
PMC5444155
DOI:
10.1128/AAC.02699-16
[Indexed for MEDLINE]
Free PMC Article

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