Abstract
Microsporidia are obligate intracellular, spore-forming parasitic fungi which are grouped with the Cryptomycota. They are both opportunistic pathogens in humans and emerging veterinary pathogens. In humans, they cause chronic diarrhea in immune-compromised patients and infection is associated with increased mortality. Besides their role in pébrine in sericulture, which was described in 1865, the prevalence and severity of microsporidiosis in beekeeping and aquaculture has increased markedly in recent decades. Therapy for these pathogens in medicine, veterinary, and agriculture has become a recent focus of attention. Currently, there are only a few commercially available antimicrosporidial drugs. New therapeutic agents are needed for these infections and this is an active area of investigation. In this article we provide a comprehensive summary of the current as well as several promising new agents for the treatment of microsporidiosis including: albendazole, fumagillin, nikkomycin, orlistat, synthetic polyamines, and quinolones. Therapeutic targets which could be utilized for the design of new drugs are also discussed including: tubulin, type 2 methionine aminopeptidase, polyamines, chitin synthases, topoisomerase IV, triosephosphate isomerase, and lipase. We also summarize reports on the utility of complementary and alternative medicine strategies including herbal extracts, propolis, and probiotics. This review should help facilitate drug development for combating microsporidiosis.
Highlights
Microsporidia are a diverse group of obligate intracellular pathogens phylogenetically related to the Cryptomycota, they form a basal branch on the phylogenic tree of fungi (James et al, 2013)
Fumagillin has a broader antimicrosporidial activity compared to albendazole as it can inhibit Encephalitozoon spp., V. corneae, and Ent. bieneusi, while albendazole has limited activity against V. corneae and Ent. bieneusi
Apart from these two well studied targets, more therapeutic targets are still required for microsporidiosis drug development
Summary
Microsporidia are a diverse group of obligate intracellular pathogens phylogenetically related to the Cryptomycota, they form a basal branch on the phylogenic tree of fungi (James et al, 2013). The host range of microsporidia extends from protists to vertebrates (James et al, 2013). These organisms have several adaptations to intracellular life including having mitochondrial remnants. All microsporidia have a dormant extracellular spore stage with a limiting spore wall and the spore contains a specialized invasion organelle (the polar tube) and the infective sporoplasm. The polar tube extrudes (germinates) allowing the microsporidia to inject the sporoplasm into host cells and start to proliferate intracellularly (Weidner, 1976)
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