학술논문

Identification of MMV Malaria Box Inhibitors of Perkinsus marinus Using an ATP-Based Bioluminescence Assay
Document Type
Academic Journal
Source
PLoS ONE. October 22, 2014, Vol. 9 Issue 10
Subject
Plasmodium falciparum
Malaria
Health
Science and technology
Language
English
ISSN
1932-6203
Abstract
"Dermo" disease caused by the protozoan parasite Perkinsus marinus (Perkinsozoa) is one of the main obstacles to the restoration of oyster populations in the USA. Perkinsus spp. are also a concern worldwide because there are limited approaches to intervention against the disease. Based on the phylogenetic affinity between the Perkinsozoa and Apicomplexa, we exposed Perkinsus trophozoites to the Medicines for Malaria Venture Malaria Box, an open access compound library comprised of 200 drug-like and 200 probe-like compounds that are highly active against the erythrocyte stage of Plasmodium falciparum. Using a final concentration of 20 [micro]M, we found that 4 days after exposure 46% of the compounds were active against P. marinus trophozoites. Six compounds with IC.sub.50 in the [micro]M range were used to compare the degree of susceptibility in vitro of eight P. marinus strains from the USA and five Perkinsus species from around the world. The three compounds, MMV666021, MMV665807 and MMV666102, displayed a uniform effect across Perkinsus strains and species. Both Perkinsus marinus isolates and Perkinsus spp. presented different patterns of response to the panel of compounds tested, supporting the concept of strain/species variability. Here, we expanded the range of compounds available for inhibiting Perkinsus proliferation in vitro and characterized Perkinsus phenotypes based on their resistance to six compounds. We also discuss the implications of these findings in the context of oyster management. The Perkinsus system offers the potential for investigating the mechanism of action of the compounds of interest.
Author(s): Yesmalie Alemán Resto [sup.2] , José A. Fernández Robledo [sup.1] [sup.*] Introduction Perkinsus marinus and Perkinsus chesapeaki cause Dermo disease in oysters and clams in the USA. Described in [...]