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从一名先天性感染患者中分离出的高致病性克氏锥虫菌株的分子与生物学特性

Molecular and biological characterization of a highly pathogenic Trypanosoma cruzi strain isolated from a patient with congenital infection.

作者信息

Gulin Julián Ernesto Nicolás, Bisio Margarita, Rocco Daniela Marisa, Altcheh Jaime, Solana María Elisa, García-Bournissen Facundo

机构信息

Servicio de Parasitología y enfermedad de Chagas - Hospital General de Niños "Dr. Ricardo Gutiérrez", Gallo 1330, CP: 1425, Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

Servicio de Parasitología y enfermedad de Chagas - Hospital General de Niños "Dr. Ricardo Gutiérrez", Gallo 1330, CP: 1425, Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

出版信息

Exp Parasitol. 2018 Mar;186:50-58. doi: 10.1016/j.exppara.2018.02.002. Epub 2018 Feb 13.

Abstract

Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of hosts have been characterized, there is a lack of information about biological features from vertically transmitted strains. We describe the molecular and biological characteristics of the T. cruzi VD strain isolated from a congenital Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 μM and 6.19 μM respectively, while inhibitory concentrations for intracellular amastigotes were 0.24 μM for BZ, and 0.66 μM for NFX. Biological behavior of VD strain was studied in a mouse model of acute infection, resulting in high levels of parasitemia and mortality with a rapid clearence of bloodstream trypomastigotes when treated with BZ or NFX, preventing mortality and reducing parasitic load and intensity of inflammatory infiltrate in skeletal and cardiac muscle. Treatment-induced parasitological cure, evaluated after immunossupression were 41% and 35% for BZ and NFX treatment respectively, suggesting a partial response to these drugs in elimination of parasite burden. This exhaustive characterization of this T. cruzi strain provides the basis for inclusion of this strain in a panel of reference strains for drug screening and adds a new valuable tool for the study of experimental T. cruzi infection.

摘要

尽管已经对从多种宿主中分离出的许多克氏锥虫(T. cruzi)菌株进行了表征,但关于垂直传播菌株的生物学特征的信息却很缺乏。我们描述了从一名先天性恰加斯病患者分离出的克氏锥虫VD菌株的分子和生物学特征。VD菌株被归类为离散型单位(DTU)TcVI;对硝呋替莫(NFX)和苯硝唑(BZ)的体外敏感性分别为2.88μM和6.19μM,而细胞内无鞭毛体的抑制浓度对于BZ为0.24μM,对于NFX为0.66μM。在急性感染的小鼠模型中研究了VD菌株的生物学行为,结果导致高寄生虫血症水平和死亡率,在用BZ或NFX治疗时血流中锥鞭毛体迅速清除,预防了死亡并降低了骨骼肌和心肌中的寄生虫负荷以及炎症浸润强度。免疫抑制后评估的治疗诱导的寄生虫学治愈,BZ和NFX治疗分别为41%和35%,表明这些药物在消除寄生虫负担方面有部分反应。对该克氏锥虫菌株的全面表征为将该菌株纳入药物筛选参考菌株库提供了基础,并为实验性克氏锥虫感染的研究增加了一个新的有价值的工具。

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