Didier Elizabeth S
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA.
Acta Trop. 2005 Apr;94(1):61-76. doi: 10.1016/j.actatropica.2005.01.010.
Microsporidia have emerged as causes of infectious diseases in AIDS patients, organ transplant recipients, children, travelers, contact lens wearers, and the elderly. These organisms are small single-celled, obligate intracellular parasites that were considered to be early eukaryotic protozoa but were recently reclassified with the fungi. Of the 14 species of microsporidia currently known to infect humans, Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common causes of human infections and are associated with diarrhea and systemic disease. Species of microsporidia infecting humans have been identified in water sources as well as in wild, domestic, and food-producing farm animals, raising concerns for waterborne, foodborne, and zoonotic transmission. Current therapies for microsporidiosis include albendazole which is a benzimidazole that inhibits microtubule assembly and is effective against several microsporidia, including the Encephalitozoon species, but is less effective against E. bieneusi. Fumagillin, an antibiotic and anti-angiogenic compound produced by Aspergillus fumigatus, is more broadly effective against Encephalitozoon spp. and Enterocytozoon bieneusi but is toxic when administered systemically to mammals. Gene target studies have focused on methionine aminopeptidase 2 (MetAP2) for characterizing the mechanism of action and for identifying more effective, less toxic fumagillin-related drugs. Polyamine analogues have shown promise in demonstrating anti-microsporidial activity in culture and in animal models, and a gene encoding topoisomerase IV was identified in Vittaforma corneae, raising prospects for studies on fluoroquinolone efficacy against microsporidia.
微孢子虫已成为艾滋病患者、器官移植受者、儿童、旅行者、隐形眼镜佩戴者及老年人感染性疾病的病因。这些生物是小型单细胞专性细胞内寄生虫,曾被认为是早期真核原生动物,但最近被重新归类为真菌。在目前已知感染人类的14种微孢子虫中,比氏肠微孢子虫和肠道脑炎微孢子虫是人类感染最常见的病因,与腹泻和全身性疾病相关。已在水源以及野生、家养和食用农产品农场动物中发现感染人类的微孢子虫种类,这引发了对水传播、食物传播和人畜共患病传播的担忧。目前治疗微孢子虫病的方法包括阿苯达唑,它是一种苯并咪唑,可抑制微管组装,对包括脑炎微孢子虫属在内的几种微孢子虫有效,但对比氏肠微孢子虫效果较差。烟曲霉素是烟曲霉产生的一种抗生素和抗血管生成化合物,对脑炎微孢子虫属和比氏肠微孢子虫更具广泛疗效,但对哺乳动物全身给药时有毒性。基因靶点研究集中在甲硫氨酸氨基肽酶2(MetAP2)上,以表征其作用机制并鉴定更有效、毒性更低的烟曲霉素相关药物。多胺类似物在培养物和动物模型中已显示出抗微孢子虫活性的前景,并且在角膜维氏孢子虫中鉴定出一种编码拓扑异构酶IV的基因,这为研究氟喹诺酮对微孢子虫的疗效带来了希望。