Microsporidians of the genus Encephalitozoon are an important cause of disease in immunocompromised patients, and there are currently no completely effective treatments. The present study investigated the viability and infectivity of spores of Encephalitozoon cuniculi that had been exposed to resveratrol (RESV), a natural phytoalexin found in grapes and red wine. RESV at 50 M showed significant sporicidal activity, and at 10 to 50 M it reduced the capacity of the spores to infect dog kidney epithelial cells of the MDCK line. At 10 M RESV also significantly inhibited intracellular development of the parasite, without affecting host cell viability. These results suggest that RESV may be useful in the treatment of Encephalitozoon infections.Microsporidians are ubiquitous small intracellular sporeforming pathogens that infect a wide range of vertebrate and invertebrate species, including humans, and that are an increasingly significant cause of disease in immunocompromised patients (36). To date, more than 1,200 species within 144 genera have been described (24). Species of the genera Nosema, Vittaforma, Brachiola, Pleistophora, Encephalitozoon, Enterocytozoon, Septata (now reclassified as Encephalitozoon), and Trachipleistophora have been found in human infections (38). Encephalitozoon cuniculi is commonly found in domestic rabbits and rodents, and also occurs in dogs and other canids and primates, including humans (32,34,36,40). Currently, no completely effective treatment exists for human microsporidiosis. The most widely used drugs for the treatment of microsporidiosis in animals and humans are albendazole and fumagillin (11,25). However, infections show variable responses to these drugs: albendazole appears to show consistent efficacy against Encephalitozoon but is variable in its efficacy against Enterocytozoon, though fumagillin appears to be effective against both species of Encephalitozoon and Enterocytozoon (7,25). Resveratrol (3,4Ј,5-trihydroxystilbene) (RESV), a natural phytoalexin produced by certain spermatophytes in response to infection by phytopathogenic microorganisms and found in grapes and grape products such as red wine, has known anticancer and anti-inflammatory effects (13,15). One probable function of RESV is to protect the plant against fungal infections (16,29), and some studies indicate that RESV may be useful for combatting human fungal pathogens (5). The microsporidians were initially considered to be protozoa but are currently considered to be parasitic fungi (4,18,23,35). In the present study we evaluated for the first time the effects of RESV on the in vitro viability and infectivity of spores of the microsporidian E. cuniculi and investigated the possible toxicity of this compound to host cells.
MATERIALS AND METHODSOrganism, cell culture, media, drugs, and chemicals. A total of 10 7 spores of a canine subtype of E. cuniculi (ATCC 50502) were grown in 75-cm 2 culture flasks (Costar) containing mycoplasma-free epithelial dog kidney cells of the MDCK line (ATCC CCL-34). The cells were ...