The Effects of Synthetic and Naturally Occurring Compounds on Microsporidian Infection in Insects

90 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1997.Microsporidia are intracellular, protist parasites infecting many animals, including insects and humans. There are currently no drugs available to cure microsporidiosis. In this thesis, I describe my work examining the effects of phytochemicals and pharmaceutical drugs on microsporidian infection in insects. Of 15 compounds tested, only xanthotoxin, a linear furanocoumarin, delayed death in Trichoplusia ni caterpillars infected with Vairimorpha sp. (T. ni isolate). This delay in death is due to indirect effects. Xanthotoxin does not directly inhibit microsporidian development or invasion of the host, but rather inhibits one of five bacteria species isolated from the midgut of T. ni. larvae. Because bacterial septicemia is often the ultimate cause of death in microsporidian-infected caterpillars, inhibition of gut bacteria can result in delayed mortality. The pharmaceutical drug albendazole is known to inhibit spore formation in some but not all species of human-infecting microsporidia. A phylogenetic screen of insect-infecting microsporidia revealed similar trends. Albendazole sensitivity was related to the type of spore packaging characteristic of the species tested. In particular, the origin of the packet envelope is indicative of albendazole sensitivity. Species forming a sporophorous vacuole (envelope of spore origin) are insensitive while species forming a parasitophorous vesicle (envelope of host origin) are susceptible. Among species producing free spores no trend was discernible; both sensitivity and insensitivity were observed. The mechanism by which albendazole inhibits spore production was examined using Endoreticulatis schubergi, a sensitive species that forms a parasitophorous vacuole in T. ni. It is evident that albendazole does not inhibit the initial invasion of host tissue. When albendazole is present during inoculation and subsequently removed from the diet at 2-day intervals, spores are present in host tissue 9 days post-inoculation. When larvae are inoculated under drug-free conditions and albendazole is subsequently added to the diet at 2-day intervals, atypical spores are formed in those larvae that received albendazole during the sporogonic cycle. Ultrastructurally, these spores show an atypically formed polar filament and a paucity of ribosomes associated with the envelope. Albendazole may be interfering with tubulin synthesis associated with formation of these structures.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD