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 µM, we found that 4 days after exposure 46% of the compounds were active against P. marinus trophozoites. Six compounds with IC50 in the µM 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.
Highlights
Perkinsus marinus and Perkinsus chesapeaki cause Dermo disease in oysters and clams in the USA
Described in the early 1950s, Dermo disease is associated with mass mortalities of eastern oysters (Crassostrea virginica) in the Gulf Coast [1]; it is under surveillance by the World Organization for Animal Health (OIE; http://www.oie.int/; Aquatic Animal Health Code, Section 11: Diseases of Molluscs)
The effect of the drugs on P. marinus proliferation was evaluated at days 2, 4, and 8 post-exposure; it was at day 4 postexposure when the inhibitory effect(s) of most drugs tested became apparent [13]
Summary
Perkinsus marinus and Perkinsus chesapeaki cause Dermo disease in oysters and clams in the USA. Described in the early 1950s, Dermo disease is associated with mass mortalities of eastern oysters (Crassostrea virginica) in the Gulf Coast [1]; it is under surveillance by the World Organization for Animal Health (OIE; http://www.oie.int/; Aquatic Animal Health Code, Section 11: Diseases of Molluscs). P. marinus has been reported with high prevalence in oysters from eastern states with no noticeable mollusk mortality [5], and recent records of P. marinus in oysters from the West Coast of North America were not associated with mortalities [6]. In the USA, P. chesapeaki displays a high preference for infecting clams and it appears to be better adapted to lower salinities and temperatures than P. marinus [5] and recently it has been detected in cockles (Cerastoderma edule) in Europe [10]. Seven Perkinsus spp. have been described, most of them in the last decade with five of them available in in vitro culture (reviewed in [11])
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