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一种新型的CDPK1抑制剂——犊牛隐孢子虫病的潜在治疗方法?

A novel CDPK1 inhibitor--a potential treatment for cryptosporidiosis in calves?

作者信息

Lendner Matthias, Böttcher Denny, Delling Cora, Ojo Kayode K, Van Voorhis Wesley C, Daugschies Arwid

机构信息

Institut für Parasitologie, Universität Leipzig, An den Tierkliniken 35, 04103, Leipzig, Germany,

出版信息

Parasitol Res. 2015 Jan;114(1):335-6. doi: 10.1007/s00436-014-4228-7. Epub 2014 Nov 15.

Abstract

Cryptosporidium parvum is a zoonotic agent that infects humans and animals occasionally causing severe, watery diarrhoea. In immunocompetent hosts, cryptosporidiosis is self-limiting but can have a fatal outcome in immunocompromised individuals. Cryptosporidium is one of the most common causes of waterborne diseases (recreational water and drinking water) in humans, a leading cause of moderate to severe childhood diarrhoea, and a major agent of diarrhoea in calves leading to high economic losses and up to 10% lethality. So far, available treatment options are insufficient for both veterinary and human clinical disease cases. Here, we report for the first time that the novel bumped kinase inhibitor (BKI) 1294 targeting the calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium is able to reduce the oocyst shedding of C. parvum by calves--its natural host--without obvious side effects.

摘要

微小隐孢子虫是一种人畜共患病原体,可感染人类和动物,偶尔会导致严重的水样腹泻。在免疫功能正常的宿主中,隐孢子虫病具有自限性,但在免疫功能低下的个体中可能会导致致命后果。隐孢子虫是人类水源性疾病(娱乐用水和饮用水)最常见的病因之一,是导致儿童中度至重度腹泻的主要原因,也是导致犊牛腹泻的主要病原体,会造成高额经济损失,致死率高达10%。到目前为止,现有的治疗方法对兽医临床病例和人类临床病例都不够充分。在此,我们首次报告,新型靶向微小隐孢子虫钙依赖性蛋白激酶1(CDPK1)的激酶抑制剂(BKI)1294能够减少微小隐孢子虫在其天然宿主犊牛中的卵囊排出,且无明显副作用。

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